Conservation and relative importance of residues across protein-protein interfaces
Conservation and relative importance of residues across protein-protein interfaces
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DOI：
10.1073/pnas.0505425102
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发表时间：
2005-10-25
影响因子：
11.1
通讯作者：
Chakrabarti, P
中科院分区：
文献类型：
--
作者：
Guharoy, M;Chakrabarti, P
被边缘包围的核心区是生物界面的特征。我们通过显示组成核心的残基的序列熵小于边缘的残基来确定核心的重要性。这种区别在单体蛋白质的晶格中形成的2倍相关的非生理界面中看不到，从而提供了一种从蛋白质分子的晶体结构表征低聚状态的方法。这种方法比那些依赖于界面和蛋白质表面其余部分的序列熵比较的方法更好，特别是在表面含有额外结合位点的情况下。一个很好的近似是，对于位于核心的残基，由于络合而损失的可达表面积与通过丙氨酸扫描诱变获得的Delta Delta G值(每埋表面26-38卡)之间存在相关性，而这种关系对于边缘残基是不可分辨的。然而，如果残基参与了界面上的氢键，则稳定的程度是被残基掩埋的非极性表面积的每1埃2 52卡/摩尔。与早先使用的氨基酸分类不同，基于环境的残基分组在核心和边缘之间的序列熵方面产生了更好的区分。
A core region surrounded by a rim characterizes biological interfaces. We ascertain the importance of the core by showing the sequence entropies of the residues comprising the core to be smaller than those in the rim. Such a distinction is not seen in the 2-fold-related, non physiological interfaces formed in crystal lattices of monomeric proteins, thereby providing a procedure for characterizing the oligomeric state from crystal structures of protein molecules. This method is better than those that rely on the comparison of the sequence entropies in the interface and the rest of the protein surface, especially in cases where the surface harbors additional binding sites. To a good approximation there is a correlation between the accessible surface area lost because of complexation and Delta Delta G values obtained through alanine-scanning mutagenesis (26-38 cal per angstrom 2 of the surface buried) for residues located in the core, a relationship that is not discernable for rim residues. If, however, a residue participates in hydrogen bonding across the interface, the extent of stabilization is 52 cal/mol per 1 angstrom 2 of the nonpolar surface area buried by the residue. As opposed to an amino acid classification used earlier, an environment-based grouping of residues yields a better discrimination in the sequence entropy between the core and the rim.