研究者詳細 - 寺田　智樹

論文 - 寺田　智樹

分割表示 34 件中 1 - 20 件目／全件表示 >>

Landscape-Based View on the Stepping Movement of Myosin VI 招待有り査読有り国際共著

Terada, TP; Nie, QM; Sasai, M

JOURNAL OF PHYSICAL CHEMISTRY B 126 巻 ( 38 ) 頁： 7262 - 7270 2022年9月

Folding pathway of a multidomain protein depends on its topology of domain connectivity 査読有り

Takashi Inanami, Tomoki P. Terada, Masaki Sasai

Proceedings of the National Academy of Sciences of the United States of America 111 巻 ( 45 ) 頁： 15969 - 15974 2014年9月

Coupling of Lever Arm Swing and Biased Brownian Motion in Actomyosin 査読有り国際共著

Qing-Miao Nie, Akio Togashi, Takeshi N. Sasaki, Mitsunori Takano, Masaki Sasai, Tomoki P. Terada

PLoS Computational Biology 10 巻 ( 4 ) 頁： e1003552, 1-13 2014年4月

Time Scales in Epigenetic Dynamics and Phenotypic Heterogeneity of Embryonic Stem Cells 査読有り

Masaki Sasai, Yudai Kawabata, Koh Makishi, Kazuhito Itoh, Tomoki P. Terada

PLoS Computational Biology 9 巻 ( 12 ) 頁： e1003380,1-17 2013年12月

担当区分：最終著者記述言語：英語掲載種別：研究論文（学術雑誌）

A remarkable feature of the self-renewing population of embryonic stem cells (ESCs) is their phenotypic heterogeneity: Nanog and other marker proteins of ESCs show large cell-to-cell variation in their expression level, which should significantly influence the differentiation process of individual cells. The molecular mechanism and biological implication of this heterogeneity, however, still remain elusive. We address this problem by constructing a model of the core gene-network of mouse ESCs. The model takes account of processes of binding/unbinding of transcription factors, formation/dissolution of transcription apparatus, and modification of histone code at each locus of genes in the network. These processes are hierarchically interrelated to each other forming the dynamical feedback loops. By simulating stochastic dynamics of this model, we show that the phenotypic heterogeneity of ESCs can be explained when the chromatin at the Nanog locus undergoes the large scale reorganization in formation/dissolution of transcription apparatus, which should have the timescale similar to the cell cycle period. With this slow transcriptional switching of Nanog, the simulated ESCs fluctuate among multiple transient states, which can trigger the differentiation into the lineage-specific cell states. From the simulated transitions among cell states, the epigenetic landscape underlying transitions is calculated. The slow Nanog switching gives rise to the wide basin of ESC states in the landscape. The bimodal Nanog distribution arising from the kinetic flow running through this ESC basin prevents transdifferentiation and promotes the definite decision of the cell fate. These results show that the distribution of timescales of the regulatory processes is decisively important to characterize the fluctuation of cells and their differentiation process. The analyses through the epigenetic landscape and the kinetic flow on the landscape should provide a guideline to engineer cell differentiation.

DOI： 10.1371/journal.pcbi.1003380

Unidirectional Brownian motion observed in an in silico single molecule experiment of an actomyosin motor 査読有り

Mitsunori Takano, Tomoki P. Terada, Masaki Sasai

Proceedings of the National Academy of Sciences of the United States of America 107 巻 ( 17 ) 頁： 7769 - 7774 2010年4月

記述言語：英語掲載種別：研究論文（学術雑誌）

The actomyosin molecular motor, the motor composed of myosin II and actin filament, is responsible for muscle contraction, converting chemical energy into mechanical work. Although recent single molecule and structural studies have shed new light on the energy-converting mechanism, the physical basis of the molecular-level mechanism remains unclear because of the experimental limitations. To provide a clue to resolve the controversy between the lever-arm mechanism and the Brownian ratchet-like mechanism, we here report an in silico single molecule experiment of an actomyosin motor. When we placed myosin on an actin filament and allowed myosin to move along the filament, we found that myosin exhibits a unidirectional Brownian motion along the filament. This unidirectionality was found to arise from the combination of a nonequilibrium condition realized by coupling to the ATP hydrolysis and a ratchet-like energy landscape inherent in the actin-myosin interaction along the filament, indicating that a Brownian ratchet-like mechanism contributes substantially to the energy conversion of this molecular motor.

DOI： 10.1073/pnas.0911830107

Correlation between evolutionary structural development and protein folding 査読有り

Chioko Nagao, Tomoki P. Terada, Tetsuya Yomo, Masaki Sasai

Proceedings of the National Academy of Sciences of the United States of America 102 巻 ( 52 ) 頁： 18950 - 18955 2005年12月

記述言語：英語掲載種別：研究論文（学術雑誌）

Evolution should have played important roles in determining folding mechanisms and structures of proteins. In this article we discuss how the folding mechanisms had been affected by the early stage of evolution through which the uniqueness of structure had developed. Although the process of such early-time evolution has remained a mystery, a plausible scenario is that the evolution of proteins toward the ordered structures was guided by functional selection pressure as demonstrated in vitro and in silico. We examine the in silico functional selection of sequences and show that there is a significant correlation between two different processes toward the unique 3D structure, the evolutionary development of structure through sequence selection, and the folding process of the resultant sequence. This finding could be rephrased as protein folding recapitulates the emergence of topology in the molecular evolution. The correlation suggests a guideline for engineering foldable proteins.

DOI： 10.1073/pnas.0509163102

Conformational change of actomyosin complex drives the multiple stepping movement 査読有り

Tomoki P. Terada, Masaki Sasai, Tetsuya Yomo

Proceedings of the National Academy of Sciences of the United States of America 99 巻 ( 14 ) 頁： 9202-9206 2002年6月

担当区分：筆頭著者,　責任著者記述言語：英語掲載種別：研究論文（学術雑誌）

Actin-myosin (actomyosin) generates mechanical force by consuming ATP molecules. We apply the energy landscape perspective to address a controversial issue as to whether the myosin head moves with multiple steps after a single ATP hydrolysis or only a single mechanical event of the lever-arm swinging follows a single ATP hydrolysis. Here we propose a theoretical model in which the refolding of the partially unfolded actomyosin complex and the movement of the myosin head along the actin filament are coupled. A single ATP hydrolysis is followed by the formation of a high free-energy partially unfolded actomyosin complex, which then gradually refolds with a concomitant multiple stepping movement on the way to the lowest free-energy rigor state. The model quantitatively explains the single-molecular observation of the multiple stepping movement and is consistent with structural observations of the disorder in the actomyosin-binding process. The model also explains the observed variety in dwell time before each step, which is not accounted for by previous models, such as the lever-arm or ratchet models.

DOI： 10.1073/pnas.132711799

A Landscape-Based View on the Stepping Movement of Myosin VI 国際共著

Tomoki P. Terada, Qing-Miao Nie, Masaki Sasai

Biophysical Journal 118 巻 ( 3 ) 頁： 436A - 437A 2020年2月

A landscape-based view on the stepping movement of myosin VI 国際共著

T. P. Terada, Q. M. Nie, M. Sasai

European Biophysics Journal with Biophysics Letters 48 巻 ( Supplement 1 ) 頁： S234 - S234 2019年7月

Single-molecular and ensemble-level oscillations of cyanobacterial circadian clock 査読有り

Sumita Das, Tomoki P. Terada, Masaki Sasai

Biophysics and Physicobiology 15 巻頁： 136 - 150 2018年5月

Role of ATP Hydrolysis in Cyanobacterial Circadian Oscillator 査読有り

Sumita Das, Tomoki P. Terada, Masaki Sasai

Scientific Reports 7 巻頁： 17469 2017年12月

Cooperativity and modularity in protein folding 招待有り査読有り

Masaki Sasai, George Chikenji, Tomoki P. Terada

Biophysics and Physicobiology 13 巻頁： 281 - 293 2016年11月

Importance of consensus region of multiple-ligand templates in a virtual screening method 査読有り

Tatsuya Okuno, Koya Kato, Shintaro Minami, Tomoki P. Terada, Masaki Sasai, George Chikenji

Biophysics and Physicobiology 13 巻頁： 149 - 156 2016年7月

真核細胞のルースな遺伝子制御とクロマチン動態招待有り査読有り

笹井理生, 寺田智樹

生物物理 56 巻 ( 2 ) 頁： 106 - 108 2016年3月

ランドスケープ描像で見る細胞分化の物理招待有り査読有り

寺田智樹

日本物理学会誌 70 巻 ( 10 ) 頁： 765 - 769 2015年10月

VS-APPLE: A Virtual Screening Algorithm Using Promiscuous Protein–Ligand Complexes 査読有り

55 巻 ( 6 ) 頁： 1108 - 1119 2015年6月

アクトミオシンの粗視化モデル解析：モーター機能におけるループの柔らかさの重要性招待有り査読有り

寺田智樹

生物物理 55 巻 ( 3 ) 頁： 148 - 150 2015年5月

Conformational flexibility of loops of myosin enhances the global bias in the actin-myosin interaction landscape 招待有り査読有り

Qing-Miao Nie, Masaki Sasai, Tomoki P. Terada

Physical Chemistry Chemical Physics 16 巻 ( 14 ) 頁： 6441-6447 2014年1月

担当区分：最終著者,　責任著者記述言語：英語掲載種別：研究論文（学術雑誌）

A long-standing controversy on the mechanism of an actomyosin motor is the role of the Brownian motion of the myosin head in force generation. In order to shed light on this problem, we calculate free-energy landscapes of interaction between an actin filament and the head (S1) of myosin II by using a coarse-grained model of actomyosin. The results show that the free-energy landscape has a global gradient toward the strong-binding site on actin filament, which explains the biased Brownian motion of myosin S1 observed in a single-molecule experiment [Kitamura et al., Nature, 1999, 397, 129 and Biophysics, 2005, 1, 1]. The distinct global gradient in the landscape is brought about only when the conformation of loop 2 at the actin interface of myosin S1 is flexible. The conformational flexibility of loop 3 also contributes to the gradient in the landscape by compensating the role of loop 2. Though the structure of loop 2 is expanded in the weak-binding state, loop 2 shows the larger fluctuation of compaction and expansion due to the actin-myosin interactions as myosin S1 moves toward the strong-binding site on actin filament. Hence, the increase in the compaction-expansion fluctuation of loop 2, the stronger binding of myosin to actin, and the biased Brownian motion of myosin S1 are coupled with each other and should take place in a concurrent way. This predicted coupling should provide opportunities to further test the hypothesis of the biased Brownian motion in actomyosin.

DOI： 10.1039/C3CP54464H

Entropic Mechanism of Allosteric Communication in Conformational Transitions of Dihydrofolate Reductase. 招待有り査読有り

Tomoki P. Terada, Toru Kimura, Masaki Sasai

The Journal of Physical Chemistry B 117 巻 ( 42 ) 頁： 12864 - 12877 2013年5月

担当区分：筆頭著者,　責任著者記述言語：英語掲載種別：研究論文（学術雑誌）

The mechanism of allosteric conformational transitions of Escherichia coli dihydrofolate reductase (DHFR) is investigated theoretically by applying a newly developed coarse-grained model. Functional forms of interaction potentials in the model depend on the local structural environments around those interactions to represent the many-residue effects due to atomic packing in each local region, and hence, this model is called "the chameleon model". The chameleon model consistently describes the free-energy landscape of two conformational transitions in the catalytic cycle of DHFR, which we call conformational transition 1 (CT1) and conformational transition 2 (CT2); CT1 is accompanied by the hydride transfer reaction, and CT2 is accompanied by the product ligand release. The transition state of CT1 is entropically stabilized by the disordering of loops at the peripheral regions of the protein, which enhances the positively correlated fluctuations at the center part of the protein, showing that the allosteric communication between distant regions through the central region is intrinsically associated with the entropic stabilization of the transition state. The transition state of CT2 is entropically stabilized through the mechanism that enhances the breathing motion of two domains, showing that the difference in the distribution of interactions brings about the difference in the transition mechanism between CT1 and CT2. The chameleon model opens a way to consistently describe the dynamical energy landscape of enzymatic reactions.

DOI： 10.1021/jp402071m

Dynamical Modeling of Three-Dimensional Genome Organization in Interphase Budding Yeast 査読有り

Naoko Tokuda, Tomoki P. Terada, Masaki Sasai

Biophysical Journal 102 巻 ( 2 ) 頁： 296 - 304 2012年1月

記述言語：英語掲載種別：研究論文（学術雑誌）

Eukaryotic genome is organized in a set of chromosomes each of which consists of a chain of DNA and associated proteins. Processes involving DNA such as transcription, duplication, and repair, therefore, should be intrinsically related to the three-dimensional organization of the genome. In this article, we develop a computational model of the three-dimensional organization of the haploid genome of interphase budding yeast by regarding chromosomes as chains moving under the constraints of nuclear structure and chromatin-chromatin interactions. The simulated genome structure largely fluctuates with the diffusive movement of chromosomes. This fluctuation, however, is not completely random, as parts of chromosomes distribute in characteristic ways to form "territories" in the nucleus. By suitably taking account of constraints arising from the data of the chromosome-conformation-capture measurement, the model explains the observed fluorescence data of chromosome distributions and motions.

DOI： 10.1016/j.bpj.2011.12.005

　前のページ - 次のページ　

<寺田 智樹>

論文 - 寺田 智樹

<寺田　智樹>

論文 - 寺田　智樹