Updated on 2024/04/01

写真a

 
HIBINO Emi
 
Organization
Graduate School of Pharmaceutical Sciences Department of Basic Medicinal Sciences Structural Biology Assistant Professor
Title
Assistant Professor
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Profile
タンパク質構造に着目したタンパク質ータンパク質間、またはタンパク質ーリガンド間相互作用の研究をしています。また、凝集性のタンパク質も研究対象としています。溶液NMRによる残基レベルでの解析により、創薬応用または生命現象解明につなげたいと考えています。
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Degree 1

  1. 博士 (薬科学) ( 2017.3   京都大学 ) 

Research Interests 6

  1. アミロイド

  2. intrinsically disordered proteins

  3. protein interaction

  4. Alzheimer's disease

  5. p53

  6. NMR

Research Areas 3

  1. Life Science / Biophysics

  2. Life Science / Pharmaceutical analytical chemistry and physicochemistry

  3. Life Science / Biophysics

Current Research Project and SDGs 1

  1. がん抑制タンパク質p53に着目した新規抗がん薬の開発

Research History 4

  1. Nagoya University   Graduate School of Pharmaceutical Science   Assistant Professor

    2022.4

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  2. Shiga University of Medical Science   Molecular Neuroscience Research Center

    2020.6

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  3. Nagoya University   Graduate School of Pharmaceutical Science   Designated assistant professor

    2020.6 - 2022.3

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  4. Shiga University of Medical Science   Designated assistant professor

    2017.4 - 2020.5

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    Country:Japan

Education 2

  1. 京都大学大学院   薬学研究科

    2011.4 - 2017.3

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  2. Kyoto University   Faculty of Pharmaceutical Sciences

    2007.4 - 2011.3

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Professional Memberships 7

  1. 日本生化学会

  2. 日本生物物理学会

  3. PROTEIN SCIENCE SOCIETY OF JAPAN

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  4. 日本核磁気共鳴学会

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  5. 日本薬学会

  6. THE JAPANESE BIOCHEMICAL SOCIETY

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  7. THE BIOPHYSICAL SOCIETY OF JAPAN

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Committee Memberships 2

  1. 日本生物物理学会   日本生物物理学会 2023年分野別専門委員  

    2023.4 - 2024.3   

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    Committee type:Academic society

  2. CIBoG卓越大学院プログラム   運営担当(メンター教員)  

    2020.6   

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    Committee type:Other

Awards 2

  1. 愛知県若手研究者イノベーション創出奨励事業 第18回わかしゃち奨励賞 基礎研究部門 優秀賞

    2024.1   愛知県   新規がん診断薬・治療薬開発を志向したp53凝集体分析法開発

    日比野絵美

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    Award type:Award from publisher, newspaper, foundation, etc.  Country:Japan

  2. 2023 Travel Award

    2023.2   Biophysical Society  

    Emi Hibino

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Papers 23

  1. A Cost-Effective Immobilization Method for MBP Fusion Proteins on Microtiter Plates Using a Gelatinized Starch–Agarose Mixture and Its Application for Convenient Protein–Protein Interaction Analysis Reviewed

    Yuri Emoto, Ryoya Katayama, Emi Hibino, Sho Ishihara, Natsuko Goda, Takeshi Tenno, Yoshihiro Kobashigawa, Hiroshi Morioka, Hidekazu Hiroaki

    Methods and Protocols   Vol. 6 ( 3 ) page: 44 - 44   2023.4

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    Language:English   Publishing type:Research paper (scientific journal)   Publisher:MDPI AG  

    The detection and quantification of protein–protein interactions (PPIs) is a crucial technique that often involves the use of recombinant proteins with fusion protein tags, such as maltose-binding protein (MBP) and glutathione-S-transferase (GST). In this study, we improved the cohesive and sticky properties of gelatinized starch by supplementing it with agarose, resulting in a harder gel that could coat the bottom of a microtiter plate. The resulting gelatinized starch/agarose mixture allowed for the efficient immobilization of MBP-tagged proteins on the coated plates, enabling the use of indirect ELISA-like PPI assays. By using the enzymatic activity of GST as an indicator, we succeeded in determining the dissociation constants between MBP-tagged and GST-tagged proteins on 96-well microtiter plates and a microplate reader without any expensive specialized equipment.

    DOI: 10.3390/mps6030044

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  2. Analysis and comparison of amorphous& amyloid aggregates of the tumor suppressor p53

    Hibino, E; Tenno, T; Hiroaki, H

    BIOPHYSICAL JOURNAL   Vol. 122 ( 3 ) page: 351A - 351A   2023.2

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  3. Moesin-ezrin-radixin-like protein merlin: Its conserved and distinct functions from those of ERM proteins. Reviewed International journal

    Yosuke Senju, Emi Hibino

    Biochimica et biophysica acta. Biomembranes   Vol. 1865 ( 2 ) page: 184076 - 184076   2022.10

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    DOI: 10.1016/j.bbamem.2022.184076

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  4. Relevance of Amorphous and Amyloid-Like Aggregates of the p53 Core Domain to Loss of its DNA-Binding Activity Reviewed International journal

    Emi Hibino, Takeshi Tenno, Hidekazu Hiroaki

    Frontiers in Molecular Biosciences   Vol. 9   page: 869851 - 869851   2022.4

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    Authorship:Lead author   Language:English   Publishing type:Research paper (scientific journal)   Publisher:Frontiers Media SA  

    The anti-oncogenic protein p53 is a transcription factor that prevents tumorigenesis by inducing gene repair proteins or apoptosis under DNA damage. Since the DNA-binding domain of p53 (p53C) is aggregation-prone, the anti-oncogenic function of p53 is often lost in cancer cells. This tendency is rather severe in some tumor-related p53 mutants, such as R175H. In this study, we examined the effect of salts, including KCl and sugars, on the aggregation of p53C by monitoring two distinct aggregates: amorphous-like and amyloid-like. The amorphous aggregates are detectable with 8-(phenylamino)-1-naphthalenesulfonic acid (ANS) fluorescence, whereas the amyloid aggregates are sensitive to thioflavin-T (ThT) fluorescence. We found that KCl inhibited the formation of amorphous aggregates but promoted the formation of amyloid aggregates in a p53C R175H mutant. The salts exhibited different effects against the wild-type and R175H mutants of p53C. However, the ratio of ANS/ThT fluorescence for the wild-type and R175H mutant remained constant. KCl also suppressed the structural transition and loss of the DNA-binding function of p53C. These observations indicate the existence of multiple steps of p53C aggregation, probably coupled with the dissociation of Zn. Notably, amorphous aggregates and amyloid aggregates have distinct properties that could be discriminated by various small additives upon aggregation.

    DOI: 10.3389/fmolb.2022.869851

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  5. A special issue of the Australian society for Biophysics.

    Dos Remedios C, Cranfield C, Whelan D, Cox C, Shearwin K, Ho J, Allen T, Shibuya R, Hibino E, Hayashi K, Li A

    Biophysical reviews   Vol. 14 ( 1 ) page: 1 - 2   2022.2

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    Language:English   Publishing type:Research paper (scientific journal)   Publisher:Biophysical Reviews  

    On behalf of the Australian Society for Biophysics (ASB) and the Editors of this Special Issue, I would like to express our appreciation to Editor-in-Chief, Damien Hall, for arranging the publication of this Special Issue. The ASB is about five times smaller than our sister the Biophysical Society for Japan (BSJ) and tenfold smaller than the US Biophysical Society (USBS), but our meetings are notable because of the encouragement the Society gives to emerging biophysicists. It can be a terrifying experience for a PhD student to have to face a roomful of professors and senior academics, but invariably they appreciate the experience. Another feature of the ASB meetings is the inclusion of contributions from the Asian Pacific region. We now have formal ties with our New Zealand colleagues and our meetings with the BSJ contain joint sessions (see below). In 2020, despite the impact of COVID-19 (see Adam Hill’s Commentary), there is a joint session with the University of California Davis. This Special Issue comprises 2 Editorials, 3 Commentaries, and 25 reviews.

    DOI: 10.1007/s12551-022-00936-8

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  6. Potential of rescue and reactivation of tumor suppressor p53 for cancer therapy

    Hibino, E; Hiroaki, H

    BIOPHYSICAL REVIEWS   Vol. 14 ( 1 ) page: 267 - 275   2022.2

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    The tumor suppressor protein p53, a transcription product of the anti-oncogene TP53, is a critical factor in preventing cellular cancerization and killing cancer cells by inducing apoptosis. As a result, p53 is often referred to as the “guardian of the genome.” Almost half of cancers possess genetic mutations in the TP53 gene, and most of these mutations result in the malfunction of p53, which promotes aggregation. In some cases, the product of the TP53 mutant allele shows higher aggregation propensity; the mutant co-aggregates with the normal (functional) p53 protein, thus losing cellular activity of the p53 guardian. Cancer might also progress because of the proteolytic degradation of p53 by activated E3 ubiquitination enzymes, MDM2 and MDM4. The inhibition of the specific interaction between MDM2 (MDM4) and p53 also results in increased p53 activity in cancer cells. Although the molecular targets of the drugs are different, two drug discovery strategies with a common goal, “rescuing p53 protein,” have recently emerged. To conduct this approach, various biophysical methods of protein characterization were employed. In this review, we focus on these two independent strategies based on the unique biophysical features of the p53 protein.

    DOI: 10.1007/s12551-021-00915-5

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  7. Bex1 is essential for ciliogenesis and harbours biomolecular condensate-forming capacity Reviewed International journal

    Emi Hibino, Yusuke Ichiyama, Atsushi Tsukamura, Yosuke Senju, Takao Morimune, Masahito Ohji, Yoshihiro Maruo, Masaki Nishimura, Masaki Mori

    BMC Biology   Vol. 20 ( 1 ) page: 42 - 42   2022.2

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    Authorship:Lead author   Language:English   Publishing type:Research paper (scientific journal)   Publisher:Springer Science and Business Media LLC  

    Abstract

    Background

    Primary cilia are sensory organelles crucial for organ development. The pivotal structure of the primary cilia is a microtubule that is generated via tubulin polymerization reaction that occurs in the basal body. It remains to be elucidated how molecules with distinct physicochemical properties contribute to the formation of the primary cilia.

    Results

    Here we show that brain expressed X-linked 1 (Bex1) plays an essential role in tubulin polymerization and primary cilia formation. The Bex1 protein shows the physicochemical property of being an intrinsically disordered protein (IDP). Bex1 shows cell density-dependent accumulation as a condensate either in nucleoli at a low cell density or at the apical cell surface at a high cell density. The apical Bex1 localizes to the basal body. Bex1 knockout mice present ciliopathy phenotypes and exhibit ciliary defects in the retina and striatum. Bex1 recombinant protein shows binding capacity to guanosine triphosphate (GTP) and forms the condensate that facilitates tubulin polymerization in the reconstituted system.

    Conclusions

    Our data reveals that Bex1 plays an essential role for the primary cilia formation through providing the reaction field for the tubulin polymerization.

    DOI: 10.1186/s12915-022-01246-x

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    Other Link: https://link.springer.com/article/10.1186/s12915-022-01246-x/fulltext.html

  8. Direct Inhibition of the First PDZ Domain of ZO-1 by Glycyrrhizin is a Possible Mechanism of Tight Junction Opening of Caco-2 Cells. Reviewed International journal

    Emi Hibino, Natsuko Goda, Misaki Hisada, Takeshi Tenno, Hidekazu Hiroaki

    Food & Function   Vol. 13 ( 4 ) page: 1953 - 1964   2022

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    Glycyrrhizin (GL) is known to exhibit a variety of useful pharmacological activities, including anti-inflammation, anti-hepatotoxicity, and enhancement of intestinal drug absorption. GL has been reported to modify the assembly of actin filaments, thereby modulating tight junction (TJ) integrity, but the detailed molecular mechanisms of this remain unclear. In this study, we first found that GL binds to the first PDZ domain of zonula occludens-1 (ZO-1(PDZ1)) through NMR experiments. The structure of the GL-ZO-1(PDZ1) complex was then constructed using HADDOCK with the transferred nuclear Overhauser effect-based inter-hydrogen distance constraints as well as restrictions on the interfacial residues identified from 1H-15N HSQC spectral changes. We identified the relevant interactions between the glucuronate-2 moiety of GL and the carboxylate binding loop of the ligand binding site of ZO-1(PDZ1). We further examined the interaction of ZO-1(PDZ1) with glycyrrhetinic acid and with GA-3-monoglucuronide and observed a much lower affinity for each than for that with GL, with good agreement with the model. The other contacts found in the model were examined by using an amino acid substitution mutant of ZO-1(PDZ1). Finally, we reproduced the experiments reported by Sakai et al. in which high-dose GL prolonged the TJ-opening mediated with sodium deoxycholate as indicated by reduced transepithelial electrical resistance.

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  9. A cryptic phosphate-binding pocket on the SPFH domain of human stomatin that regulates a novel fibril-like self-assembly. Reviewed International journal

    Koki Kataoka, Shota Suzuki, Takeshi Tenno, Natsuko Goda, Emi Hibino, Atsunori Oshima, Hidekazu Hiroaki

    Current research in structural biology   Vol. 4   page: 158 - 166   2022

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    Human stomatin (hSTOM) is a component of the membrane skeleton of erythrocytes that maintains the membrane's shape and stiffness through interconnecting spectrin and actin. hSTOM is a member of the protein family that possesses a single stomatin/prohibitin/flotillin/HflK (SPFH) domain at the center of the molecule. Although SPFH domain proteins are widely distributed from archaea to mammals, the detailed function of the domain remains unclear. In this study, we first determined the solution structure of the SPFH domain of hSTOM (hSTOM(SPFH)) via NMR. The solution structure of hSTOM(SPFH) is essentially identical to the already reported crystal structure of the STOM SPFH domain (mSTOM(SPFH)) of mice, except for the existence of a small hydrophilic pocket on the surface. We identified this pocket as a phosphate-binding site by comparing its NMR spectra with and without phosphate ions. Meanwhile, during the conventional process of protein NMR analysis, we eventually discovered that hSTOM(SPFH) formed a unique solid material after lyophilization. This lyophilized hSTOM(SPFH) sample was moderately slowly dissolved in a physiological buffer. Interestingly, it was resistant to dissolution against the phosphate buffer. We then found that the lyophilized hSTOM(SPFH) formed a fibril-like assembly under electron microscopy. Finally, we succeeded in reproducing this fibril-like assembly of hSTOM(SPFH) using a centrifugal ultrafiltration device, thus demonstrating that the increased protein concentration may promote self-assembly of hSTOM(SPFH) into fibril forms. Our observations may help understand the molecular function of the SPFH domain and its involvement in protein oligomerization as a component of the membrane skeleton. (245 words).

    DOI: 10.1016/j.crstbi.2022.05.002

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  10. 1Structural and Functional Analysis of Glycyrrhizin Bound to the Scaffold Protein ZO1-PDZ1 of Tight Junctions

    Hibino, E; Hisada, M; Goda, N; Tenno, T; Hiroaki, H

    PROTEIN SCIENCE   Vol. 30   page: 119 - 119   2021.10

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  11. Announcing the call for the Special Issue on "The Australian Society for Biophysics (ASB) - 2021 Meeting".

    Cranfield C, Whelan D, Cox C, Shearwin K, Ho J, Allen T, Shibuya R, Hibino E, Hayashi K, Dos Remedios C, Li A

    Biophysical reviews   Vol. 13 ( 4 ) page: 485 - 486   2021.8

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    This Commentary describes a call for submissions for the upcoming Special Issue focused on the research topics presented at the Australian Society of Biophysics (ASB) in 2020 and 2021. Submissions from past and present ASB members who could not attend these meetings are also welcome as contributions to this special issue.

    DOI: 10.1007/s12551-021-00813-w

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  12. Extracellular Release of ILEI/FAM3C and Amyloid-β Is Associated with the Activation of Distinct Synapse Subpopulations Reviewed

    Masaki Nakano, Yachiyo Mitsuishi, Lei Liu, Naoki Watanabe, Emi Hibino, Saori Hata, Takashi Saito, Takaomi C. Saido, Shigeo Murayama, Kensaku Kasuga, Takeshi Ikeuchi, Toshiharu Suzuki, Masaki Nishimura

    Journal of Alzheimer's Disease   Vol. 80 ( 1 ) page: 1 - 16   2021.1

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    Background: Brain amyloid-β (Aβ) peptide is released into the interstitial fluid (ISF) in a neuronal activity-dependent manner, and Aβ deposition in Alzheimer’s disease (AD) is linked to baseline neuronal activity. Although the intrinsic mechanism for Aβ generation remains to be elucidated, interleukin-like epithelial-mesenchymal transition inducer (ILEI) is a candidate for an endogenous Aβ suppressor. Objective: This study aimed to access the mechanism underlying ILEI secretion and its effect on Aβ production in the brain. Methods: ILEI and Aβ levels in the cerebral cortex were monitored using a newly developed ILEI-specific ELISA and in vivo microdialysis in mutant human Aβ precursor protein-knockin mice. ILEI levels in autopsied brains and cerebrospinal fluid (CSF) were measured using ELISA. Results: Extracellular release of ILEI and Aβ was dependent on neuronal activation and specifically on tetanus toxin-sensitive exocytosis of synaptic vesicles. However, simultaneous monitoring of extracellular ILEI and Aβ revealed that a spontaneous fluctuation of ILEI levels appeared to inversely mirror that of Aβ levels. Selective activation and inhibition of synaptic receptors differentially altered these levels. The evoked activation of AMPA-type receptors resulted in opposing changes to ILEI and Aβ levels. Brain ILEI levels were selectively decreased in AD. CSF ILEI concentration correlated with that of Aβ and were reduced in AD and mild cognitive impairment. Conclusion: ILEI and Aβ are released from distinct subpopulations of synaptic terminals in an activity-dependent manner, and ILEI negatively regulates Aβ production in specific synapse types. CSF ILEI might represent a surrogate marker for the accumulation of brain Aβ.

    DOI: 10.3233/jad-201174

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  13. Potential of rescue and reactivation of tumor suppressor p53 for cancer therapy. Invited Reviewed

    Hibino E, Hiroaki H

    Biophysical Reviews     2021

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  14. FAM3C in Alzheimer's disease. A risk-related molecule and potential therapeutic target. Reviewed

    Nishimura M, Watanabe N, Mitsuishi Y, Hibino E, Nakano M, Liu L, Sugi T

    Neuroscience of Dementia     page: in press   2020

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  15. A novel mode of interaction between intrinsically disordered proteins Reviewed

    Emi Hibino, Masaru Hoshino

    Biophysics and Physicobiology   Vol. 17 ( 0 ) page: 86 - 93   2020

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    Authorship:Lead author   Language:English   Publishing type:Research paper (scientific journal)   Publisher:Biophysical Society of Japan  

    <p>An increasing number of proteins, which have neither regular secondary nor well-defined tertiary structures, have been found to be present in cells. The structure of these proteins is highly flexible and disordered under physiological (native) conditions, and they are called “intrinsically disordered” proteins (IDPs). Many of the IDPs are involved in interactions with other biomolecules such as DNA, RNA, carbohydrates, and proteins. While these IDPs are largely unstructured by themselves, marked conformational changes often occur upon binding to an interacting partner, which is known as the “coupled folding and binding mechanism”, which enable them to change the conformation to become compatible with the shape of the multiple target biomolecules. We have studied the structure and interaction of eukaryotic transcription factors Sp1 and TAF4, and found that both of them have long intrinsically disordered regions (IDRs). One of the IDRs in Sp1 exhibited homo-oligomer formation. In addition, the same region was used for the interaction with another IDR found in the TAF4 molecule. In both cases, we have not detected any significant conformational change in that region, suggesting a prominent and novel binding mode for IDPs/IDRs, which are not categorized by the well-accepted concept of the coupled folding and binding mechanism.</p>

    DOI: 10.2142/biophysico.bsj-2020012

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  16. FAM3C in Alzheimer’s disease. A risk-related molecule and potential therapeutic target. Reviewed

    Nishimura M, Watanabe N, Mitsuishi Y, Hibino E, Nakano M, Liu L, Sugi T

    Neuroscience of Dementia   Vol. 2   page: 293 - 307   2020

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  17. FAM3C in Alzheimer's disease

    Masaki Nishimura, Naoki Watanabe, Emi Hibino, Masaki Nakano, Yachiyo Mitsuishi, Lei Liu, Takuma Sugi

    Genetics, Neurology, Behavior, and Diet in Dementia     page: 293 - 307   2020

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    DOI: 10.1016/b978-0-12-815868-5.00019-0

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  18. Lipid class composition of membrane and raft fractions from brains of individuals with Alzheimer's disease. Reviewed International journal

    Akihiro Kawatsuki, Shin-Ya Morita, Naoki Watanabe, Emi Hibino, Yachiyo Mitsuishi, Takuma Sugi, Shigeo Murayama, Masaki Nishimura

    Biochemistry and biophysics reports   Vol. 20 ( 100704 ) page: 100704 - 100704   2019.12

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    Perturbation of the homeostasis of brain membrane lipids has been implicated in the pathomechanism of Alzheimer's disease (AD). The ε4 allele of the apolipoprotein E gene (APOE) confers an increased risk, in a dosage-dependent manner, for brain amyloid-β accumulation and the development of sporadic AD. An effect of the APOE genotype on brain lipid homeostasis may underlie the AD risk associated with the ε4 allele. In this research, we examined an effect of APOE ε4 on the lipid class composition of crude membranes and raft-enriched fractions of brains. We applied enzymatic reaction-based methods for the quantification of phosphatidylcholine, phosphatidylethanolamine, phosphatidylserine, phosphatidic acid, and sphingomyelin. Our results indicate that brain lipid class composition was neither significantly altered in AD subjects nor affected by the presence of the APOE ε4 allele.

    DOI: 10.1016/j.bbrep.2019.100704

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  19. 大脳皮質におけるILEI/FAM3CおよびAβの間質液への分泌様式に関する比較検討 Reviewed

    中野 将希, 三ツ石 弥千代, 渡邊 直希, 日比野 絵美, 斉藤 貴志, 西道 隆臣, 鈴木 利治, 西村 正樹

    Dementia Japan   Vol. 33 ( 4 ) page: 514 - 514   2019.10

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  20. Novel Interaction Mechanism between the Intrinsically Disordered Proteins

    Emi HIBINO, Masaru HOSHINO

    Seibutsu Butsuri   Vol. 59 ( 4 ) page: 202 - 204   2019

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    Language:Japanese   Publishing type:Research paper (scientific journal)   Publisher:Biophysical Society of Japan  

    DOI: 10.2142/biophys.59.202

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  21. Identification of heteromolecular binding sites in transcription factors Sp1 and TAF4 using high-resolution nuclear magnetic resonance spectroscopy Reviewed

    Emi Hibino, Rintaro Inoue, Masaaki Sugiyama, Jun Kuwahara, Katsumi Matsuzaki, Masaru Hoshino

    PROTEIN SCIENCE   Vol. 26 ( 11 ) page: 2280 - 2290   2017.11

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    The expression of eukaryotic genes is precisely controlled by interactions between general transcriptional factors and promoter-specific transcriptional activators. The fourth element of TATA-box binding protein-associated factor (TAF4), an essential subunit of the general transcription factor TFIID, serves as a coactivator for various promoter-specific transcriptional regulators. Interactions between TAF4 and site-specific transcriptional activators, such as Sp1, are important for regulating the expression levels of genes of interest. However, only limited information is available on the molecular mechanisms underlying the interactions between these transcriptional regulatory proteins. We herein analyzed the interaction between the transcriptional factors Sp1 and TAF4 using high-resolution solution nuclear magnetic resonance spectroscopy. We found that four glutamine-rich (Q-rich) regions in TAF4 were largely disordered under nearly physiological conditions. Among them, the first Q-rich region in TAF4 was essential for the interaction with another Q-rich region in the Sp1 molecule, most of which was largely disordered. The residues responsible for this interaction were specific and highly localized in a defined region within a range of 20-30 residues. Nevertheless, a detailed analysis of C-13-chemical shift values suggested that no significant conformational change occurred upon binding. These results indicate a prominent and exceptional binding mode for intrinsically disordered proteins other than the well-accepted concept of coupled folding and binding."

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  22. Interaction between intrinsically disordered regions in transcription factors Sp1 and TAF4 Reviewed

    Emi Hibino, Rintaro Inoue, Masaaki Sugiyama, Jun Kuwahara, Katsumi Matsuzaki, Masaru Hoshino

    PROTEIN SCIENCE   Vol. 25 ( 11 ) page: 2006 - 2017   2016.11

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    The expression of eukaryotic genes is precisely controlled by specific interactions between general transcription initiation factors and gene-specific transcriptional activators. The general transcription factor TFIID, which plays an essential role in mediating transcriptional activation, is a multisubunit complex comprising the TATA box-binding protein (TBP) and multiple TBP-associated factors (TAFs). On the other hand, biochemical and genetic approaches have shown that the promoter-specific transcriptional activator Sp1 has the ability to interact with one of the components of TFIID, the TBP-associated factor TAF4. We herein report the structural details of the glutamine-rich domains (Q-domains) of Sp1 and TAF4 using circular dichroism (CD) and heteronuclear magnetic resonance (NMR) spectroscopy. We found that the two Q-domains of Sp1 and four Q-domains of TAF4 were disordered under physiological conditions. We also quantitatively analyzed the interaction between the Q-domains of Sp1 and TAF4 by NMR and surface plasmon resonance, and detected a weak but specific association between them. Nevertheless, a detailed analysis of CD spectra suggested that any significant conformational change did not occur concomitantly with this association, at least at the level of the overall secondary structure. These results may represent a prominent and exceptional binding mode for the IDPs, which are not categorized in a well-accepted concept of "coupled folding and binding."

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  23. Interaction between isolated transcriptional activation domains of Sp1 revealed by heteronuclear magnetic resonance Reviewed

    Naoko Hiramatsu, Emi Hibino, Katsumi Matsuzaki, Jun Kuwahara, Masaru Hoshino

    PROTEIN SCIENCE   Vol. 21 ( 10 ) page: 1481 - 1488   2012.10

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    The promoter-specific transcription factor Sp1 is expressed ubiquitously, and plays a primary role in the regulation of the expression of many genes. Domains A and B located in the N-terminal half of the protein are characterized by glutamine-rich (Q-rich) sequences. These Q-rich domains have been shown to be involved in the interaction between Sp1 and different classes of nuclear proteins, such as TATA-binding protein associated factors. Furthermore, the self-association of Sp1 via Q-rich domains is also important for the regulation of transcriptional activity. It has been considered that an Sp1 molecule bound to a distal GC-box synergistically interacts with another Sp1 molecule at a proximal binding site. Although the formation of multimers via Q-rich domains seems functionally important for Sp1, little is known about the structural and physicochemical nature of the interaction between Q-rich domains. We analyzed the structural details of isolated glutamine-rich B (QB) domains of Sp1 by circular dichroism (CD), analytical ultracentrifugation, and heteronuclear magnetic resonance spectroscopy (NMR). We found the isolated QB domains to be disordered under all conditions examined. Nevertheless, a detailed analysis of NMR spectra clearly indicated interaction between the domains. In particular, the C-terminal half was responsible for the self-association. Furthermore, analytical ultracentrifugation demonstrated weak but significant interaction between isolated QB domains. The self-association between QB domains would be responsible, at least in part, for the formation of multimers by full-length Sp1 molecules that has been proposed to occur during transcriptional activation.

    DOI: 10.1002/pro.2137

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MISC 11

  1. Analysis and comparison of amorphous &amp; amyloid aggregates of the tumor suppressor p53

    Hibino E., Tenno T., Hiroaki H.

    Biophysical journal   Vol. 122 ( 3S1 )   2023.2

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    DOI: 10.1016/j.bpj.2022.11.1949

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  2. A special issue of the Australian society for Biophysics. International journal

    Cristobal Dos Remedios, Charles Cranfield, Donna Whelan, Charles Cox, Keith Shearwin, Joshua Ho, Toby Allen, Risa Shibuya, Emi Hibino, Kumiko Hayashi, Amy Li

    Biophysical reviews   Vol. 14 ( 1 ) page: 1 - 2   2022.2

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    On behalf of the Australian Society for Biophysics (ASB) and the Editors of this Special Issue, I would like to express our appreciation to Editor-in-Chief, Damien Hall, for arranging the publication of this Special Issue. The ASB is about five times smaller than our sister the Biophysical Society for Japan (BSJ) and tenfold smaller than the US Biophysical Society (USBS), but our meetings are notable because of the encouragement the Society gives to emerging biophysicists. It can be a terrifying experience for a PhD student to have to face a roomful of professors and senior academics, but invariably they appreciate the experience. Another feature of the ASB meetings is the inclusion of contributions from the Asian Pacific region. We now have formal ties with our New Zealand colleagues and our meetings with the BSJ contain joint sessions (see below). In 2020, despite the impact of COVID-19 (see Adam Hill's Commentary), there is a joint session with the University of California Davis. This Special Issue comprises 2 Editorials, 3 Commentaries, and 25 reviews.

    DOI: 10.1007/s12551-022-00936-8

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  3. Announcing the call for the Special Issue on “The Australian Society for Biophysics (ASB) – 2021 Meeting”

    Charles Cranfield, Donna Whelan, Charles Cox, Keith Shearwin, Joshua Ho, Toby Allen, Risa Shibuya, Emi Hibino, Kumiko Hayashi, Cristobal dos Remedios, Amy Li

    Biophysical Reviews   Vol. 13 ( 4 ) page: 485 - 486   2021.6

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    Language:English   Publisher:Springer Science and Business Media LLC  

    DOI: 10.1007/s12551-021-00813-w

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    Other Link: https://link.springer.com/article/10.1007/s12551-021-00813-w/fulltext.html

  4. 大脳皮質におけるILEI/FAM3CおよびAβの間質液への分泌様式に関する比較検討

    中野 将希, 三ツ石 弥千代, 渡邊 直希, 日比野 絵美, 斉藤 貴志, 西道 隆臣, 鈴木 利治, 西村 正樹

    Dementia Japan   Vol. 33 ( 4 ) page: 514 - 514   2019.10

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  5. Physicochemical study on ILEI suppressing amyloid-β generation

    Emi Hibino

    KURNS Progress Report 2018     2019

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  6. アミロイドβタンパク質産生量を減少させるタンパク質ILEIの物理科学的解析

    KURNS-EKR-3     2019

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  7. Aβ産生抑制タンパク質ILEI/FAM3Cの転写制御機構の解析

    渡邊 直希, 日比野 絵美, 中野 将希, 庄司 航, 杉 拓磨, 西村 正樹

    Dementia Japan   Vol. 32 ( 3 ) page: 432 - 432   2018.9

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  8. Aβ産生抑制タンパク質ILEIの構造および機能の解析

    日比野 絵美, 杉田 昌岳, 三ツ石 弥千代, 渡邊 直希, 中野 将希, 杉 拓磨, 西村 正樹

    Dementia Japan   Vol. 32 ( 3 ) page: 432 - 432   2018.9

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  9. Aβ産生抑制タンパク質ILEIの構造解析に基づく機能メカニズムの検討

    日比野 絵美, 森田 修平, 野村 礼, 川月 章弘, 渡邊 直希, 西村 正樹

    Dementia Japan   Vol. 31 ( 4 ) page: 571 - 571   2017.10

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  10. 孤発性アルツハイマー病のリスク遺伝子TM2D3の機能解析

    川月 章弘, 渡邊 直希, 日比野 絵美, 野村 礼, 西村 正樹

    Dementia Japan   Vol. 31 ( 4 ) page: 561 - 561   2017.10

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  11. Glutamine-rich activation domain of transcription factor Sp1-biochemical activity and structure

    Jun Kuwahara, Chisana Uwatoko, Emi Hibino, Katsumi Matsuzaki, Masaru Hoshino

    PROTEIN SCIENCE   Vol. 24   page: 312 - 312   2015.10

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Presentations 27

  1. Preparation and analysis of aggregates formed by the tumor suppressor protein p53 Invited

    Emi Hibino, Reiji Hijikata, Takeshi Tenno, Hidekazu Hiroaki

    2023.11.16 

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    Event date: 2023.11

    Language:English   Presentation type:Oral presentation (general)  

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  2. ANALYSIS AND COMPARISON OF AMORPHOUS & AMYLOID AGGREGATES OF THE TUMOR SUPPRESSOR P53.

    Emi HIBINO, Takeshi TENNO, Hidekazu HIROAKI

    67th Biophysical Society Annual Meeting  2023.2.21 

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    Event date: 2023.2

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  3. CTCFによる転移因子コード解読機構解明に向けて

    日比野 絵美, SHARIF Jafar, 一柳 健司

    第45回 日本分子生物学会年会  2022.12.1 

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    Event date: 2022.11 - 2022.12

    Language:English   Presentation type:Symposium, workshop panel (nominated)  

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  4. Roles of endogenous repetitive elements and intrinsically disordered domain proteins for 3D genome folding

    Emi HIBINO, Kenji ICHIYANAGI, Ryo ONISHI, Jafar SHARIF

    2022.11.4 

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    Event date: 2022.11

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  5. New insights into amorphous & amyloid aggregates of the tumor suppressor p53

    2022.9.30 

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    Event date: 2022.9

    Language:English   Presentation type:Poster presentation  

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  6. p53-DNA結合ドメインのアミロイド凝集体の解析に向けて

    日比野絵美

    第3回 NUSR-CeSPI 合同セミナー  2022.9.16 

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    Event date: 2022.9

    Language:English   Presentation type:Oral presentation (general)  

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  7. 液-液相分離へのNMRのアプローチを考える Invited

    日比野絵美

    第22回 若手NMR研究会  2022.9.13 

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    Event date: 2022.9

    Language:English   Presentation type:Oral presentation (invited, special)  

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  8. がん抑制タンパク質p53の凝集体形成と機能喪失は併発しない

    日比野 絵美, 天野 剛志, 廣明 秀一

    日本薬学会第142年会  2022.3.27 

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    Event date: 2022.3

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  9. Structural and Functional Analysis of Glycyrrhizin Bound to the Scaffold Protein ZO1-PDZ1 of Tight Junctions

    Emi Hibino, Misaki Hisada, Natsuko Goda, Takeshi Tenno, Hidekazu Hiroaki

    35th Virtual Anniversary Symposium of The Protein Society 

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    Event date: 2021.7

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  10. Correlation between aggregate formation and function of the tumor suppressor protein p53

    Emi Hibino, Natsuko Goda, Takeshi Tenno, Hidekazu Hiroaki

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    Event date: 2021.6

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  11. Active center of Aβ production repressor ILEI/FAM3C

    ○Emi Hibino, Masaki Nishimura

    The 58th Annual Meeting of the Biophysical Society of Japan  2020.9.16 

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    Event date: 2020.9

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  12. The interaction between transcription factors Sp1 and TAF4 via the intrinsically disordered regions. International conference

    The 9th SKO Symposium Program 

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    Event date: 2015.11

    Language:English   Presentation type:Oral presentation (general)  

    Country:Korea, Republic of  

  13. 転写因子Sp1とTAF4の天然変性領域を介した相互作用の解析

    日比野 絵美, 井上 倫太郎, 杉山 正明, 桑原 淳, 松崎 勝巳, 星野 大

    第15回日本蛋白質科学会年会  2015.6 

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    Event date: 2015.6

    Language:Japanese   Presentation type:Poster presentation  

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  14. 転写因子Sp1とTAF4の天然変性領域を介した相互作用 Invited

    日比野 絵美, 井上 倫太郎, 杉山 正明, 桑原 淳, 松崎 勝巳, 星野 大

    第52回日本生物物理学会年会 

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    Event date: 2014.9

    Language:English   Presentation type:Oral presentation (invited, special)  

    Venue:札幌   Country:Japan  

  15. 転写因子Sp1とTAF4の天然変性領域を介した相互作用 Invited

    日比野 絵美, 井上 倫太郎, 杉山 正明, 桑原 淳, 松崎 勝巳, 星野 大

    第52回日本生物物理学会年会  2014.9 

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    Event date: 2014.9

    Language:English   Presentation type:Oral presentation (invited, special)  

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  16. 転写因子Sp1とTAF4の天然変性領域を介した相互作用の解析

    日比野 絵美, 桑原 淳, 松崎 勝巳, 星野 大

    第13回日本蛋白質科学会年会  

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    Event date: 2013.6

    Language:Japanese   Presentation type:Poster presentation  

    Venue:鳥取   Country:Japan  

  17. 転写因子Sp1とTAF4の天然変性領域を介した相互作用の解析

    日比野 絵美, 桑原 淳, 松崎 勝巳, 星野 大

    第13回日本蛋白質科学会年会  2013.6 

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    Event date: 2013.6

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  18. ILEI/FAM3C Suppresses Amyloid-β Generation by a Unique Mechanism International conference

    Emi Hibino

    24th MNRC International symposium  2018.9 

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  19. Aβ産生抑制タンパク質ILEIの構造解析に基づく機能メカニズムの検討

    日比野 絵美

    第36回日本認知症学会学術集会  2017.11 

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  20. ILEI/FAM3C represses Aβ production: structural and functional properties

    Emi Hibino

    ConBio2017  2017.12 

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  21. Structure-based analysis of ILEI/FAM3C activity to inhibit Aβ generation

    ◯Emi Hibino, Masatake Sugita, Yachiyo Mitsuishi, Naoki Watanabe, Masaki Nakano, Takuma Sugi, Masaki Nishimura

    The 56th Annual Meeting of The Biophysical Society of Japan  2018.9 

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  22. Risk for Alzheimer's disease and ILEI/FAM3C that suppresses amyloid-β generation by a unique mechanism

    ◯Emi Hibino, Naoki Watanabe, Masaki Nishimura

    The 91st Annual Meeting of the Japanese Biochemical Society  2018.9 

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  23. 天然変性領域間の相互作用の物理化学的解析

    日比野 絵美

    蛋白質異常凝集研究会  2017.12 

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  24. The interaction between transcription factors Sp1 and TAF4 via the intrinsically disordered regions. International conference

    ◯Emi Hibino, Rintaro Inoue, Masaaki Sugiyama, Jun Kuwahara, Katsumi Matsuzaki, Masaru Hoshino

    The 9th SKO Symposium Program  2015.11 

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  25. グリチルリチンとタイト結合裏打ちタンパク質ZO1-PDZ1ドメインとの結合解析

    日比野絵美, 久田美咲, 合田名都子, 天野剛志, 廣明秀一

    令和2年度 生物物理中部支部講演会  2021.3 

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  26. グリチルリチンのタイト結合裏打ちタンパク質ZO1 PDZ1ドメインへの結合構造の解析

    日比野絵美, 久田美咲, 合田名都子, 天野剛志, 廣明秀一

    日本薬学会第141年会  2021.3 

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  27. Relevance of amorphous and amyloid aggregates of the p53 core domain to its DNA-binding activity

    Emi Hibino, Takeshi Tenno, Hidekazu Hiroaki

    2022.6.9 

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Research Project for Joint Research, Competitive Funding, etc. 7

  1. がん抑制タンパク質p53が形成するアミロイドに基づいたがん診断法開発

    2023.4 - 2024.3

    2022年度 (第54回) 倉田奨励金 (自然科学・工学研究部門) 

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    Authorship:Principal investigator 

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  2. がん抑制タンパク質p53のアミロイド形成機構の原子レベル解析

    2022.12 - 2023.11

    令和4年度 学術・みらい助成 

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    Authorship:Principal investigator 

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  3. 転移因子と天然変性タンパク質によるクロマチン高次構造構築原理の解明

    2022.3

    令和3年度NU部局横断イノベーション創出プロジェクト 

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    Authorship:Coinvestigator(s) 

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  4. 亜鉛イオン含有がん抑制タンパク質p53のアミロイド凝集体解析

    2022 - 2024.3

    2022年度研究助成 

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  5. がん抑制タンパク質p53の凝集制御法の確立

    2022 - 2023.3

    研究奨励金 

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  6. がん抑制タンパク質p53の機能喪失につながる新規機構解明

    2021 - 2022.3

    がんその他の悪性新生物研究助成金 

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    Authorship:Principal investigator  Grant type:Competitive

    Grant amount:\500000 ( Direct Cost: \500000 )

  7. ゲノム内在性の反復配列と天然変性タンパク質の相互作用による核内 3 次元コンパートメント形成の解析

    2021 - 2022.3

    令和3年度科学技術ハブ共同研究プログラム 

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KAKENHI (Grants-in-Aid for Scientific Research) 5

  1. がん抑制タンパク質p53の凝集制御且つ分解制御を達成する

    Grant number:23K14334  2023.4 - 2026.3

    日本学術振興会  科学研究費助成事業 若手研究  若手研究

    日比野 絵美

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    Authorship:Principal investigator  Grant type:Competitive

    Grant amount:\4680000 ( Direct Cost: \3600000 、 Indirect Cost:\1080000 )

    がん抑制タンパク質p53はがん化を防ぐ上で非常に重要な役割を果たしているが、現在まで、p53を標的とした抗がん薬の開発は難航している。p53の機能喪失経路には、凝集経路と分解経路の主に2通りある。世界的には分解経路に着目した創薬が進められており、凝集経路の研究が遅れている状況にある。p53は、DNA結合ドメインを起点としてアミロイド凝集体とアモルファス凝集体が同時に形成することがわかっている。本申請課題では、この2種類の凝集体と、さらに分解経路の3つを対象にして研究を進め、抗がん薬のリード化合物を同定することを目指す。

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  2. Analysis of a new mechanism to specifically inhibit amyloid-beta protein production

    Grant number:18K14883  2018.4 - 2022.3

    Grants-in-Aid for Scientific Research  Grant-in-Aid for Early-Career Scientists

    Hibino Emi

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    Authorship:Principal investigator 

    Grant amount:\4160000 ( Direct Cost: \3200000 、 Indirect Cost:\960000 )

    Alzheimer's disease is associated with the accumulation of amyloid-β protein (Aβ) in the brain. The secreted protein ILEI has been reported to inhibit the production of Aβ and APP-CTF, a precursor of Aβ. In this study, I first established a simple evaluation system for the Alzheimer's disease-preventive function of ILEI using cultured cells, and then used the evaluation system to identify the site that appears to be the active center of ILEI. Although ILEI is also known to cause oncogenesis, this study strongly suggests that the active centers of ILEI's inhibitory and oncogenic effects on Aβ production are separate. The results of this research will provide the foundation for the development of therapeutic and preventive drugs for Alzheimer's disease.

  3. ILEIとPresenilin-1との結合構造解析に基づくアルツハイマー病分子治療薬の設計

    2018.4 - 2019.3

    滋賀医科大学  学長裁量経費(若手萌芽研究) 

    日比野 絵美

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    Authorship:Principal investigator  Grant type:Competitive

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  4. アミロイドβタンパク質産生を特異的に抑制する新たな機序の解析

    2018 - 2020

    文部科学省  科学研究費助成事業 

    日比野 絵美

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    Authorship:Principal investigator  Grant type:Competitive

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  5. ILEIとγセクレターゼ複合体との結合構造解析に基づくアルツハイマー病分子治療薬の設計

    2017.4 - 2018.3

    滋賀医科大学  学長裁量経費(若手萌芽研究) 

    日比野 絵美

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    Authorship:Principal investigator  Grant type:Competitive

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Industrial property rights 1

  1. p53アミロイド凝集体の製造方法

    日比野絵美, 廣明秀一

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    Applicant:国立大学法人東海国立大学機構

    Application no:特願2023-077995  Date applied:2023.5

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Teaching Experience (Off-campus) 1

  1. 生理学

    京都文化医療専門学校)

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Social Contribution 1

  1. 第3回 滋賀ジュニアリサーチグラント成果発表会

    Role(s):Advisor

    リバネス  2020.2

Academic Activities 4

  1. 第45回日本分子生物学会年会 (千葉市) ワークショップ「転移因子コードによる核内相分離構造の理解」オーガナイザー

    Role(s):Panel moderator, session chair, etc.

    2022.12

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    Type:Competition, symposium, etc. 

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  2. 第2回CIBoGリトリート(第13回NAGOYAグローバルリトリート)

    2021.1

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  3. 第3回滋賀ジュニアリサーチグラント成果発表会

    Role(s):Review, evaluation

    株式会社リバネス  2020.2

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  4. Biophysical Reviews spacial issue guest editor

    Role(s):Supervision (editorial)

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