Protein-protein interactions: Coupling of structurally conserved residues and of hot spots across interfaces. implications for docking
Protein-protein interactions: Coupling of structurally conserved residues and of hot spots across interfaces. implications for docking
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DOI：
10.1016/j.str.2004.04.009
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发表时间：
2004-06-01
期刊：
影响因子：
5.7
通讯作者：
Nussinov, R
中科院分区：
文献类型：
--
作者：
Halperin, I;Wolfson, H;Nussinov, R
热点残基主要参与蛋白质-蛋白质相互作用。从统计学上讲，保守残基与热点相关，它们的出现可以区分结合位点和蛋白质表面的其余部分。在界面一侧进行了热点和守恒分析。在这里，我们表明，实验热点和保守残基往往耦合跨两链接口。有趣的是，热点和保守残基周围的局部堆积密度高于预期。我们进一步观察到局部堆积密度和实验Δ Δ G之间的相关性。有利的保守对包括Gly与芳族基团、带电和极性残基以及芳族残基偶联。值得注意的是，带电残基对的代表性不足。总体而言，蛋白质-蛋白质相互作用似乎由高和低堆积密度区域组成，热点在前者中组织。结合界面中的高局部堆积密度使人联想到蛋白质核心。
Hot spot residues contribute dominantly to protein-protein interactions. Statistically, conserved residues correlate with hot spots, and their occurrence can distinguish between binding sites and the remainder of the protein surface. The hot spot and conservation analyses have been carried out on one side of the interface. Here, we show that both experimental hot spots and conserved residues tend to couple across two-chain interfaces. Intriguingly, the local packing density around both hot spots and conserved residues is higher than expected. We further observe a correlation between local packing density and experimental DeltaDeltaG. Favorable conserved pairs include Gly coupled with aromatics, charged and polar residues, as well as aromatic residue coupling. Remarkably, charged residue couples are underrepresented. Overall, protein-protein interactions appear to consist of regions of high and low packing density, with the hot spots organized in the former. The high local packing density in binding interfaces is reminiscent of protein cores.