MRC Laboratory of Molecular Biology, Hills Road, Cambridge CB2 0QH, UK.
J Mol Biol. 2010 Nov 5;403(4):660-70. doi: 10.1016/j.jmb.2010.09.028. Epub 2010 Sep 22.
Analysis of proteins commonly requires the partition of their structure into regions such as the surface, interior, or interface. Despite the frequent use of such categorization, no consensus definition seems to exist. This study thus aims at providing a definition that is general, is simple to implement, and yields new biological insights. This analysis relies on 397, 196, and 701 protein structures from Escherichia coli, Saccharomyces cerevisiae, and Homo sapiens, respectively, and the conclusions are consistent across all three species. A threshold of 25% relative accessible surface area best segregates amino acids at the interior and at the surface. This value is further used to extend the core-rim model of protein-protein interfaces and to introduce a third region called support. Interface core, rim, and support regions contain similar numbers of residues on average, but core residues contribute over two-thirds of the contact surface. The amino acid composition of each region remains similar across different organisms and interface types. The interface core composition is intermediate between the surface and the interior, but the compositions of the support and the rim are virtually identical with those of the interior and the surface, respectively. The support and rim could thus "preexist" in proteins, and evolving a new interaction could require mutations to form an interface core only. Using the interface regions defined, it is shown through simulations that only two substitutions are necessary to shift the average composition of a 1000-Å(2) surface patch involving ∼28 residues to that of an equivalent interface. This analysis and conclusions will help understand the notion of promiscuity in protein-protein interaction networks.
蛋白质分析通常需要将其结构划分为不同区域，如表面、内部或界面。尽管这种分类经常被使用，但似乎没有一个共识的定义。因此，本研究旨在提供一个通用的、易于实现的定义，并产生新的生物学见解。该分析依赖于分别来自大肠杆菌、酿酒酵母和人类的 397196 和 701 个蛋白质结构，并且三个物种的结论是一致的。相对可及表面积的 25%是将氨基酸分隔在内部和表面的最佳阈值。该值进一步用于扩展蛋白质-蛋白质界面的核心-边缘模型，并引入第三个称为支撑的区域。界面核心、边缘和支撑区域的平均残基数相似，但核心残基贡献了超过三分之二的接触表面。每个区域的氨基酸组成在不同的生物体和界面类型之间保持相似。界面核心的组成在表面和内部之间处于中间位置，但支撑和边缘的组成与内部和表面几乎相同。因此，支撑和边缘可以“预先存在”于蛋白质中，并且进化新的相互作用可能只需要突变形成界面核心。使用定义的界面区域，通过模拟表明，只需要两个取代就可以将平均组成从一个涉及约 28 个残基的 1000Å(2)表面片段转移到等效界面。这项分析和结论将有助于理解蛋白质-蛋白质相互作用网络中的多功能性概念。
