驱动马达力学化学耦合机制研究进展

黎明; 欧阳钟灿; 舒咬根

doi:10.7498/aps.65.188702

摘要

驱动蛋白是细胞内重要的输运机器，属于平动分子马达. 它有两个主要特征，其一是持续性，马达的两个头部在交替步行时至少有一头保持与微管吸附，因此它能沿微管长距离步进而不脱轨；另一个特征是马达的力学过程和化学过程是紧耦合的，即马达每前进一步消耗一个三磷酸腺苷. 上述两个特征要求两个头部的核苷化学态及其与微管的相互作用需通过某个机构来协调统一，其中的核心问题是力学化学耦合机制，这也是所有化学驱动的分子马达的关键问题. 得益于单分子实验技术和分子动力学模拟技术的发展，驱动马达力学化学耦合机制的研究在最近十年取得了重大突破. 本文重点从运动学、动力学、协同机制和发力机制等方面介绍驱动马达基础研究的进展及面临的问题.

关键词:

Abstract

Kinesin is one of the most important linear motors for intracellular transport. It has two main features. One is its persistence: at least one head is attached to the microtubule during stepping, so that it can move a long distance before detaching. Another feature is the tight mechanochemical coupling: it consumes one adenosine-triphosphate for each step. Therefore, there should be a mechanism responsible for the coordination of the two heads to achieve the high persistence and tight coupling. The underlying mechanism is the mechanochemical coupling, which is the basic issue for all chemical-driven molecular motors. Owing to the developments of single-molecule experiments and molecular dynamics simulations, a breakthrough in the coupling mechanism has been made in recent decades. In this article, we review the progress of the relevant researches from the perspective of kinematics, energetics, coordination of two heads and force generating mechanism. We also present a personal perspective on the future studies of kinesin.

Keywords:

作者及机构信息

1.
中国科学院大学物理科学学院, 北京 100049;

2.
中国科学院理论物理研究所, 北京 100190

通信作者: 舒咬根, shuyg@itp.ac.cn

基金项目: 国家重点基础研究发展计划（批准号：2013CB932804）、国家自然科学基金（批准号：11574329，11322543，11105218）和The Joint NSFC-ISF Research Program（批准号：51561145002）资助的课题.

Authors and contacts

1.
School of Physical Sciences, University of Chinese Academy of Sciences, Beijing 100049, China;

2.
Institute of Theoretical Physics, Chinese Academy of Sciences, Beijing 100190, China

Corresponding author: Shu Yao-Gen, shuyg@itp.ac.cn

Funds: Project supported by the National Basic Research Program of China (Grant No. 2013CB932804), the National Natural Science Foundation of China (Grant Nos. 11574329, 11322543, 11105218), and the Joint NSFC-ISF Research Program (Grant No. 51561145002).

参考文献

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[69]	Shu Y G, Lai P Y 2008 J. Phys. Chem. B 112 13453
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[73]	Chowdhury D 2012 Phys. Rep. 529 1

施引文献

[1]	Shu Y G, Ouyang Z C 2007 Physics 36 735 (in Chinese) [舒咬根, 欧阳钟灿 2007 物理 36 735]
[2]	Berlinrood M, McGee-Russell S M, Allen R D 1972 J. Cell Sci. 11 875
[3]	Allen R D, Allen N S, Travis J L 1981 Cell Motil. 1 291
[4]	Allen R D, Allen N S 1983 J. Microscopy 129 3
[5]	Allen R D, Metuzals J, Tasahi I, et al. 1982 Science 218 1127
[6]	Brady S T, Lasek R J, Allen R D 1982 Science 218 1129
[7]	Allen R D, Weiss D G, Hayden J H, et al. 1985 J. Cell Biol. 100 1736
[8]	Vale R D, Schnapp B J, Reese T S, et al. 1985 Cell 40 449
[9]	Vale R D, Schnapp B J, Reese T S, et al. 1985 Cell 40 559
[10]	Vale R D, Reese T S, Sheetz M P 1985 Cell 42 39
[11]	Brady S T 1985 Nature 317 73
[12]	Lawrence C J, Dawe R K, Christie K R, et al. 2004 J. Cell Biol. 167 19
[13]	Bloom G S, Wagner M C, Pfister K K, et al. 1988 Biochemistry 27 3409
[14]	Kuznetsov S A, Vaisberg E A, Shanina N A, et al. 1988 EMBO J. 7 353
[15]	Hirokawa N, Pfister K K, Yorifuji H, et al. 1989 Cell 56 867
[16]	Song Y H, Mandelkow E 1993 PNAS. 90 1671
[17]	Kull F J, Sablin E P, Lau R, et al. 1996 Nature 380 550
[18]	Sablin E P, Kull F J, Cooke R, et al. 1996 Nature 380 555
[19]	Kozielski F, Sack S, Marx A, et al. 1997 Cell 91 985
[20]	Case R B, Pierce D W, Hom-Booher N, et al. 1997 Cell 90 959
[21]	Rice S, Lin A W, Safer D, et al. 1999 Nature 402 778
[22]	Ashkin A, Dziedzic J M, Bjorkholm J E, et al. 1986 Opt. Lett. 11 288
[23]	Ashkin A, Dziedzic J M 1987 Science 235 1517
[24]	Visscher K, Schnitzer M J, Block S M 1999 Nature 400 184
[25]	Svoboda K, Schmidt C F, Schnapp B J, et al. 1993 Nature 365 721
[26]	Hua W, Chung J, Gelles J 2002 Science 295 844
[27]	Yildiz A, Tomishige M, Vale R D, et al. 2004 Science 303 676
[28]	Schief W R, Clark R H, Crevenna A H, et al. 2004 . PNAS 101 1183
[29]	Kodera N, Yamamoto D, Ishikawa R, et al. 2010 Nature 468 72
[30]	Jlicher F, Ajdari A, Prost J 1997 Rev. Mod. Phys. 69 1269
[31]	Hua W, Young E C, Fleming M L, et al. 1997 Nature 388 390
[32]	Coy D L, Wagenbach M, Howard J 1999 J. Biol. Chem. 274 3667
[33]	Chemla Y R, Moffitt J R, Bustamante C 2008 J. Phys. Chem. 112 6025
[34]	Svoboda K, Mitra P P, Block S M 1994 PNAS 91 11782
[35]	Schnitzer M J, Block S M 1995 Cold Spring Harbor Symposia on Quantitative Biology LX 793
[36]	Schnitzer M J, Block S M 1997 Nature 388 386
[37]	Yildiz A, Tomishige M, Gennerich A, et al. 2008 Cell 134 1030
[38]	Clancy B E, Behnke-Parks W M, Andreasson J O L, et al. 2011 Nat. Struct. Mol. Biol. 18 1020
[39]	Rosenfeld S S, Fordyce P M, Jefferson G M, et al. 2003 J. Biol. Chem. 278 18550
[40]	Kawaguchi K, Ishiwata S 2001 Science 291 667
[41]	Block S M 2007 Biophys. J. 92 2986
[42]	Miyazono Y, Hayashi M, Karagiannis P, et al. 2010 EMBO J. 29 93
[43]	Hackney D D, Stock M F, Moore J, et al. 2003 Biochemistry 42 12011
[44]	Dogan M Y, Can S, Cleary F B, et al. 2015 Cell Rep. 10 1967
[45]	Hwang W, Lang M J, Karplus M 2008 Structure 16 62
[46]	Milic B, Andreasson J O, Hancock W O, et al. 2014 PNAS 111 14136
[47]	Andreasson J O, Milic B, Chen G Y, et. al. 2015 Elife Sciences 4 e07403
[48]	Mickolajczyk K J, Deffenbaugh N C, Ortega Arroyo J, et al. 2015 PNAS 112 E7186
[49]	Shu Y G, Zhang X H, Ouyang Z C, et al. 2012 J. Phys: Condens. Matter 24 035105
[50]	Bornschlgl T, Woehlke G, Rief M 2009 PNAS 106 6992
[51]	Coppin C M, Finer J T, Spudich J A, et al. 1996 PNAS 93 1913
[52]	Nishiyama M, Muto E, Inoue Y, et al. 2001 Nat. Cell Biol. 3 425
[53]	Taniguchi Y, Nishiyama M, Ishii Y, et al. 2005 Nat. Chem. Biol. 1 342
[54]	Zhang Z, Thirumalai D 2012 Structure 20 628
[55]	Wade R H, Kozielski F 2000 Nat. Struct. Biol. 7 456
[56]	Rice S, Cui Y, Sindelar C, et al. 2003 Biophys. J. 84 1844
[57]	Carter N J, Cross R A 2005 Nature 435 308
[58]	Fox R F, Choi M H 2001 Phys. Rev. E. 63 051901
[59]	Mather W H, Fox R F 2006 Biophys. J. 91 2416
[60]	Astumian R D 2015 Biophys. J. 108 291
[61]	Hopfield J J 1974 PNAS 71 4135
[62]	Khalil A S, Appleyard D C, Labno A K, et. al. 2009 PNAS 105 19247
[63]	Svoboda K, Block S M 1994 Cell 77 773
[64]	Nishiyama M, Higuchi H, Yanagida T 2002 Nat. Cell Biol. 4 790
[65]	Kolomeisky A B, Fisher M E 2007 Annu. Rev. Phys. Chem. 58 675
[66]	Liepelt S, Lipowsky R 2007 Phys. Rev. Lett. 98 258102
[67]	Hyeon C, Klumpp S, Onuchic J N 2009 Phys. Chem. Chem. Phys. 11 4899
[68]	Shu Y G, Ouyang Z C 2007 Chinese Journal of Nature 29 249 (in Chinese) [舒咬根, 欧阳钟灿 2007 自然杂志 29 249]
[69]	Shu Y G, Lai P Y 2008 J. Phys. Chem. B 112 13453
[70]	Toyabe S, Watanabe-Nakayama T, Okamoto T, et al. 2011 PNAS 108 17951
[71]	Toyabe S, Muneyuki E 2015 New J. Phys. 17 015008
[72]	Tsygankov D, Lindn M, Fisher M E 2006 Phys. Rev. E. 75 95
[73]	Chowdhury D 2012 Phys. Rep. 529 1

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