Choi Sun Shim, Li Weimin, Lahn Bruce T
Howard Hughes Medical Institute, Department of Human Genetics, University of Chicago, Chicago, Illinois 60637, USA.
Nat Genet. 2005 Dec;37(12):1367-71. doi: 10.1038/ng1685. Epub 2005 Nov 13.
The structure of a protein depends critically on the complex interactions among its amino acid residues. It has long been hypothesized that interacting residues might tend to coevolve, but it is not known whether such coevolution is a general phenomenon across the proteome. Here, we describe a novel methodology called phylogeny-aided structural analysis, which uncovers robust signals of interacting-residue coevolution in mammalian proteomes. Furthermore, this new method allows the magnitude of coevolution to be quantified. Finally, it facilitates a comprehensive evaluation of various factors that affect interacting-residue coevolution, such as the physicochemical properties of the interactions between residues, solvent accessibility of the residues and their secondary structure context.
蛋白质的结构严重依赖于其氨基酸残基之间的复杂相互作用。长期以来，人们一直推测相互作用的残基可能倾向于共同进化，但尚不清楚这种共同进化是否是整个蛋白质组中的普遍现象。在此，我们描述了一种名为系统发育辅助结构分析的新方法，该方法揭示了哺乳动物蛋白质组中相互作用残基共同进化的强烈信号。此外，这种新方法能够对共同进化的程度进行量化。最后，它有助于全面评估影响相互作用残基共同进化的各种因素，例如残基之间相互作用的物理化学性质、残基的溶剂可及性及其二级结构背景。
