Mechanical coupling in myosin V: a simulation study.
Mechanical coupling in myosin V: a simulation study.
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DOI：
10.1016/j.jmb.2009.10.029
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发表时间：
2010-01-29
影响因子：
5.6
通讯作者：
Karplus M
中科院分区：
文献类型：
--
作者：
Ovchinnikov V;Trout BL;Karplus M
肌球蛋白运动功能依赖于不同结构域之间的相互作用，这些结构域将信息从分子的一部分传递到另一部分。采用限制靶向分子动力学（RTMD）方法研究了肌球蛋白V结构域间的耦合。为了阐明由于ATP的结合而引起的构象变化的起源，靶向力被施加到小的原子集合（强制集合，FS）上，使它们从具有封闭的肌动蛋白结合裂缝的僵直构象位移到裂缝开放的僵直后构象。导致整体肌球蛋白构象发生广泛结构变化的“最小”FS由ATP、开关1和附近的HF、HG和HH螺旋组成。需要将开关2添加到强制组以实现肌动蛋白结合裂隙的完全打开。RTMD模拟揭示了（i）核苷酸结合口袋（NBP）和肌动蛋白结合裂缝（actin-binding cleft）之间、（ii）NBP和转换器之间以及（iii）肌动蛋白结合裂缝和转换器之间的机械耦合途径。由于ATP结合而导致的NBP的关闭与裂缝的打开紧密耦合，并导致开关2和SH 1螺旋之间的关键氢键（F441 N/A684 O）的断裂。肌动蛋白结合裂缝可以通过HW螺旋、中继螺旋和开关2之间的连接来介导该键的断裂。这一发现与实验研究和最近的正态模式分析是一致的。本方法有望在蛋白质结构域间偶联的研究中得到更广泛的应用。
Myosin motor function depends on the interaction between different domains that transmit information from one part of the molecule to another. The inter-domain coupling in myosin V is studied with Restrained Targeted Molecular Dynamics (RTMD) using an all-atom representation in explicit solvent. To elucidate the origin of the conformational change due to the binding of ATP, targeting forces are applied to small sets of atoms (the forcing sets, FS) in the direction of their displacement from the rigor conformation, which has a closed actin-binding cleft, to the post-rigor conformation, in which the cleft is open. The ‘minimal’ FS that results in extensive structural changes in the overall myosin conformation is comprised of the ATP, Switch 1, and the nearby HF, HG and HH helices. Addition of switch 2 to the forcing set is required to achieve a complete opening of the actin-binding cleft. The RTMD simulations reveal the mechanical coupling pathways between (i) the nucleotide-binding pocket (NBP) and the actin-binding cleft, (ii) the NBP and the converter, and (iii) the actin-binding cleft and the converter. Closing of the NBP due to ATP binding is tightly coupled to the opening of the cleft, and leads to the rupture of a key hydrogen bond (F441N/A684O) between switch 2 and the SH1 helix. The actin-binding cleft may mediate the rupture of this bond via a connection between the HW helix, the Relay helix, and Switch 2. The findings are consistent with experimental studies and a recent normal mode analysis. The present method is expected to be useful more generally in studies of inter-domain coupling in proteins.
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DOI：
10.1098/rstb.2004.1566
发表时间：
2004-12-29
期刊：
PHILOSOPHICAL TRANSACTIONS OF THE ROYAL SOCIETY OF LONDON SERIES B-BIOLOGICAL SCIENCES
影响因子：
--
作者：
Holmes, KC;Schröder, RR;Houdusse, A
通讯作者：
Houdusse, A
DOI：
10.1073/pnas.96.24.13726
发表时间：
1999-11-23
影响因子：
11.1
作者：
De La Cruz, EM;Wells, AL;Sweeney, HL
通讯作者：
Sweeney, HL
DOI：
10.1002/prot.340040208
发表时间：
1988-01-01
期刊：
PROTEINS-STRUCTURE FUNCTION AND GENETICS
影响因子：
--
作者：
BRUNGER, AT;KARPLUS, M
通讯作者：
KARPLUS, M
影响因子：
56.9
作者：
Yildiz, A;Forkey, JN;Selvin, PR
通讯作者：
Selvin, PR
影响因子：
5.7
作者：
Koppole, Sampath;Smith, Jeremy C.;Fischer, Stefan
通讯作者：
Fischer, Stefan