Origins of coevolution between residues distant in protein 3D structures
Origins of coevolution between residues distant in protein 3D structures
复制标题
DOI：
10.1073/pnas.1702664114
复制
发表时间：
2017-08-22
影响因子：
11.1
通讯作者：
Baker, David
中科院分区：
文献类型：
--
作者：
Anishchenko, Ivan;Ovchinnikov, Sergey;Baker, David
在蛋白质家族中直接共同进化的残基对在蛋白质三维结构中通常是接近的。在这里，我们研究了这种普遍趋势的例外情况——在蛋白质结构上距离较远的直接共同进化的残基对——以确定空间距离较远的残基的进化压力的起源，并了解基于接触的结构预测的错误来源。在一组4000个蛋白质家族中，我们发现25%的直接共进化残基对在蛋白质结构中间隔超过5埃，3%的蛋白质结构间隔超过15埃。大多数（91%）在5-15埃范围内的直接共进化残基对至少在一个同源结构中接触，这些例外是由于含有残基区域的家族结构变化。在大于15埃的异常中，有35%是在同源寡聚界面上，19%是由家族结构变异引起的，27%是在重复蛋白中，可能反映了比对错误。在剩余的长期异常（耦合对总数的< 1%）中，许多可以归因于低聚状态下的密切相互作用。总的来说，结果表明，直接共同进化的残基对不在重复蛋白中，在该家族中至少有一种生物相关的蛋白质构象在空间上是近端的；我们发现很少有证据表明在空间分离的变构和功能位点上残基之间存在直接耦合，或者在连接它们的假定变构途径上残基对之间存在增加的直接耦合。
Residue pairs that directly coevolve in protein families are generally close in protein 3D structures. Here we study the exceptions to this general trend-directly coevolving residue pairs that are distant in protein structures-to determine the origins of evolutionary pressure on spatially distant residues and to understand the sources of error in contact-based structure prediction. Over a set of 4,000 protein families, we find that 25% of directly coevolving residue pairs are separated by more than 5 angstrom in protein structures and 3% by more than 15 angstrom. The majority (91%) of directly coevolving residue pairs in the 5-15 angstrom range are found to be in contact in at least one homologous structure-these exceptions arise from structural variation in the family in the region containing the residues. Thirty-five percent of the exceptions greater than 15 angstrom are at homo-oligomeric interfaces, 19% arise from family structural variation, and 27% are in repeat proteins likely reflecting alignment errors. Of the remaining long-range exceptions (< 1% of the total number of coupled pairs), many can be attributed to close interactions in an oligomeric state. Overall, the results suggest that directly coevolving residue pairs not in repeat proteins are spatially proximal in at least one biologically relevant protein conformation within the family; we find little evidence for direct coupling between residues at spatially separated allosteric and functional sites or for increased direct coupling between residue pairs on putative allosteric pathways connecting them.