Faculty of Life Sciences, University of Manchester, Oxford Road, Manchester M13 9PT, UK.
J Mol Biol. 2012 Jun 22;419(5):387-96. doi: 10.1016/j.jmb.2012.03.021. Epub 2012 Apr 1.
The functional importance of protein-protein interactions indicates that there should be strong evolutionary constraint on their interaction interfaces. However, binding interfaces are frequently affected by amino acid replacements. Change due to coevolution within interfaces can contribute to variability but is not ubiquitous. An alternative explanation for the ability of surfaces to accept replacements may be that many residues can be changed without affecting the interaction. Candidates for these types of residues are those that make interchain interaction only through the protein main chain, β-carbon, or associated hydrogen atoms. Since almost all residues have these atoms, we hypothesize that this subset of interface residues may be more easily substituted than those that make interactions through other atoms. We term such interactions "residue type independent." Investigating this hypothesis, we find that nearly a quarter of residues in protein interaction interfaces make exclusively interchain residue-type-independent contacts. These residues are less structurally constrained and less conserved than residues making residue-type-specific interactions. We propose that residue-type-independent interactions allow substitutions in binding interfaces while the specificity of binding is maintained.
蛋白质-蛋白质相互作用的功能重要性表明，它们的相互作用界面应该受到强烈的进化约束。然而，结合界面经常受到氨基酸替换的影响。由于界面内的共进化而导致的变化可以导致变异性，但并非普遍存在。表面接受替换的另一种解释可能是，许多残基可以改变而不影响相互作用。这些类型的残基的候选者是那些仅通过蛋白质主链、β-碳或相关氢原子与链间相互作用的残基。由于几乎所有的残基都有这些原子，我们假设这种界面残基子集比那些通过其他原子进行相互作用的残基更容易被取代。我们将这种相互作用称为“残基类型无关”。为了研究这一假设，我们发现蛋白质相互作用界面中的近四分之一的残基只进行链间残基类型无关的接触。这些残基的结构约束性和保守性都低于残基特异性相互作用的残基。我们提出，残基类型无关的相互作用允许在保持结合特异性的同时在结合界面上进行替换。
