Conformational transitions of adenylate kinase: Switching by cracking
Conformational transitions of adenylate kinase: Switching by cracking
复制标题
DOI：
10.1016/j.jmb.2006.11.085
复制
发表时间：
2007-03-09
影响因子：
5.6
通讯作者：
Onuchic, Jose N.
中科院分区：
文献类型：
--
作者：
Whitford, Paul C.;Miyashita, Osamu;Onuchic, Jose N.
蛋白质的构象异质性通常被认为是其功能的关键。我们提出了一个粗粒度模型来探索蛋白质结构、折叠和功能之间的相互作用，该模型适用于变构或非变构蛋白质。我们利用该模型研究了腺苷酸激酶(AKE)从开放构象到闭合构象的可逆构象转变的详细机制，这一反应对蛋白质的催化功能至关重要。我们直接观察到高应变能，这似乎与功能转变过程中的局域展开有关。这项工作还证明了开放形式和封闭形式的竞争自然相互作用可以解释AKE中的大构象转变。我们进一步用一种新的测量来表征构象转变，并证明局部展开可能部分是由于竞争的蛋白质内相互作用。(C)2006爱思唯尔有限公司。保留所有权利。
Conformational heterogeneity in proteins is known to often be the key to their function. We present a coarse grained model to explore the interplay between protein structure, folding and function which is applicable to allosteric or non-allosteric proteins. We employ the model to study the detailed mechanism of the reversible conformational transition of Adenylate Kinase (AKE) between the open to the closed conformation, a reaction that is crucial to the protein's catalytic function. We directly observe high strain energy which appears to be correlated with localized unfolding during the functional transition. This work also demonstrates that competing native interactions from the open and closed form can account for the large conformational transitions in AKE. We further characterize the conformational transitions with a new measure and demonstrate that local unfolding may be due, in part, to competing intra-protein interactions. (c) 2006 Elsevier Ltd. All rights reserved.