Nucleotide-Dependent Lateral and Longitudinal Interactions in Microtubules
Nucleotide-Dependent Lateral and Longitudinal Interactions in Microtubules
复制标题
DOI：
10.1016/j.jmb.2013.03.029
复制
发表时间：
2013-06-26
影响因子：
5.6
通讯作者：
Voth, Gregory A.
中科院分区：
文献类型：
--
作者：
Grafmueller, Andrea;Noya, Eva G.;Voth, Gregory A.
微管（MT）的稳定性与结合在β-微管蛋白上的鸟苷三磷酸核苷酸（NT）的水解有关。然而，NT状态影响MT晶格中接触稳定性的分子机制仍然难以捉摸。在这里，我们提出了大规模的原子模拟不同的微管蛋白聚集体，包括个人二聚体，短原丝，一个小的晶格补丁，和一块MT晶格与两个无限的原丝在两个NT状态。再加上粗粒度（CG）的波动分析，这些模拟突出了几个区域的蛋白质的局部变化引起的NT状态或横向和纵向接触的聚集体。此外，CG分析提供了结构变化如何影响蛋白质之间键的指示。结果表明，一个可能的分子机制，NT状态诱导的H1-S2环的变化和更稳定的纵向键，这两者都位于H1-S2和M-环在更有利的位置，形成横向接触的一致图片。(c)2013爱思唯尔有限公司保留所有权利。
Microtubule (MT) stability is related to the hydrolysis of the guanosine triphosphate nucleotide (NT) bound to beta-tubulin. However, the molecular mechanism by which the NT state influences the stability of the contacts in the MT lattice remains elusive. Here, we present large-scale atomistic simulations of different tubulin aggregates, including individual dimers, short protofilaments, a small lattice patch, and a piece of the MT lattice with two infinite protofilaments in both NT states. Together with a coarse-grained (CG) analysis of the fluctuations, these simulations highlight several regions of the protein where local changes are induced by the NT state or by the lateral and longitudinal contacts in the aggregates. Additionally, the CG analysis provides an indication of how the structural changes affect the bonds between the proteins. The results suggest a consistent picture of a possible molecular mechanism by which the NT state induces changes in the H1-S2 loop and more stable longitudinal bonds, both of which locate the H1-S2 and M-loop in more favorable positions to form lateral contacts. (c) 2013 Elsevier Ltd. All rights reserved.