Department of Chemistry, James Franck Institute, and Computation Institute, University of Chicago, 5735 S. Ellis Avenue, Chicago, IL 60637, USA.
Structure. 2011 Mar 9;19(3):409-17. doi: 10.1016/j.str.2010.12.020.
The complex polymerization dynamics of the microtubule (MT) plus end are closely linked to the hydrolysis of the GTP nucleotide bound to the β-tubulin. The destabilization is thought to be associated with the conformational change of the tubulin dimers from the straight conformation in the MT lattice to a curved conformation. It remains under debate whether this transformation is directly related to the nucleotide state, or a consequence of the longitudinal or lateral contacts in the MT lattice. Here, we present large-scale atomistic simulations of short tubulin protofilaments with both nucleotide states, starting from both extreme conformations. Our simulations indicate that both interdimer and intradimer contacts in both GDP and GTP-bound tubulin dimers and protofilaments in solution bend. There are no observable differences between the mesoscopic properties of the contacts in GTP and GDP-bound tubulin or the intradime and interdimer interfaces.
微管（MT）加端的复杂聚合动力学与结合在β-微管蛋白上的 GTP 核苷酸的水解密切相关。这种去稳定作用被认为与微管蛋白二聚体从 MT 晶格中的直线构象到弯曲构象的构象变化有关。目前仍存在争议的是，这种转变是否直接与核苷酸状态有关，还是 MT 晶格中纵向或横向接触的结果。在这里，我们从两种极端构象出发，对具有两种核苷酸状态的短微管原丝进行了大规模的原子模拟。我们的模拟表明，在溶液中，GDP 和 GTP 结合的微管蛋白二聚体以及原丝中的二聚体间和二聚体内的接触都发生了弯曲。在 GDP 和 GTP 结合的微管蛋白或二聚体内部和二聚体之间的界面中，接触的介观性质没有观察到明显的差异。
