Coevolutionary constraints in the sequence-space of macromolecular complexes reflect their self-assembly pathways
Coevolutionary constraints in the sequence-space of macromolecular complexes reflect their self-assembly pathways
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DOI：
10.1002/prot.25292
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发表时间：
2017-07-01
影响因子：
2.9
通讯作者：
Kundu, Sudip
中科院分区：
文献类型：
--
作者：
Mallik, Saurav;Kundu, Sudip
生物分子亚基自组装成功能性大分子复合物的顺序是否在它们的序列空间中留下印记？在这里，我们证明了大分子复合物自组装的时间顺序可以有效地捕获使用景观的残留水平的共同进化的约束。这种预测能力的共同进化的约束是无关的结构，功能和系统发育分类的复杂和化学计量和四元排列的组成单体。结合这一结果与一些结构属性估计从晶体结构数据，我们发现的迹象表明，较强的共同进化的约束在接口形成的装配层次结构早期可能促进协调固定的突变，导致高亲和力结合更高的表面积，增加表面的互补性和升高的分子接触的数量相比，形成晚在组装。蛋白质2017; 85：1183-1189。(c)2017年Wiley Periodicals，Inc.
Is the order in which biomolecular subunits self-assemble into functional macromolecular complexes imprinted in their sequence-space? Here, we demonstrate that the temporal order of macromolecular complex self-assembly can be efficiently captured using the landscape of residue-level coevolutionary constraints. This predictive power of coevolutionary constraints is irrespective of the structural, functional, and phylogenetic classification of the complex and of the stoichiometry and quaternary arrangement of the constituent monomers. Combining this result with a number of structural attributes estimated from the crystal structure data, we find indications that stronger coevolutionary constraints at interfaces formed early in the assembly hierarchy probably promotes coordinated fixation of mutations that leads to high-affinity binding with higher surface area, increased surface complementarity and elevated number of molecular contacts, compared to those that form late in the assembly. Proteins 2017; 85:1183-1189. (c) 2017 Wiley Periodicals, Inc.