Multivariate analysis of conserved sequence-structure relationships in kinesins: Coupling of the active site and a tubulin-binding sub-domain
Multivariate analysis of conserved sequence-structure relationships in kinesins: Coupling of the active site and a tubulin-binding sub-domain
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DOI：
10.1016/j.jmb.2007.02.049
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发表时间：
2007-05-18
影响因子：
5.6
通讯作者：
Cross, Robert A.
中科院分区：
文献类型：
--
作者：
Grant, Barry J.;McCammon, J. Andrew;Cross, Robert A.
一个广泛的计算分析可用的序列和晶体结构的数据被用来确定功能上重要的残基相互作用内的马达结构域的驱动蛋白分子马达。主成分分析表明，所有目前的驱动蛋白晶体结构驻留在两个主要的构象，这在活性位点不同，并在一个微管结合子域相对于一个刚性的中央核心的位置之一。该亚结构域由二级结构元件α 4-loop 12-α 5-loop 13组成，并含有保守的亲水性表面补丁，其可能参与与微管的强结合。子域运动的铰链点位于位置292处的保守甘氨酸附近。统计偶联分析揭示了一个网络的共同发展的位置，连接该地区的核苷酸结合位点，通过一个高度保守的组氨酸在开关I环。这些数据是一致的模型，其中的核苷酸状态的活性位点之间的弱和强的结合构象，通过重新配置所确定的子域驱动蛋白的转变。我们的数据提供了一个统计支持的框架，进一步检查这个和其他结构功能关系的驱动蛋白家族。(C)2007爱思唯尔有限公司版权所有。
An extensive computational analysis of available sequence and crystal structure data was used to identify functionally important residue interactions within the motor domain of the kinesin molecular motor. Principal component analysis revealed that all current kinesin crystal structures reside in one of two main conformations, which differ at the active site, and in the position of a microtubule-binding sub-domain relative to a rigid central core. This sub-domain consists of secondary structure elements alpha 4-loop12-alpha 5-loop13 and contains a conserved hydrophilic surface patch that may be involved in strong binding to microtubules. A hinge point for the sub-domain motion lies near a conserved glycine at position 292. Statistical coupling analysis revealed a network of co-evolving positions that link this region to the nucleotide-binding site, via a highly conserved histidine in the switch I loop. The data are consistent with a model in which the nucleotide status of the active site shifts kinesin between weak and strong binding conformations via reconfiguration of the identified sub-domain. Our data provide a statistically supported framework for further examination of this and other structure-function relationships in the kinesin family. (C) 2007 Elsevier Ltd. All rights reserved.