Centre for Integrative Systems Biology and Bioinformatics, Division of Molecular Biosciences, Department of Life Sciences, Imperial College London, London SW7 2AZ, UK.
Hum Mutat. 2012 Feb;33(2):359-63. doi: 10.1002/humu.21656. Epub 2011 Dec 27.
Many nonsynonymous single nucleotide polymorphisms (nsSNPs) are disease causing due to effects at protein-protein interfaces. We have integrated a database of the three-dimensional (3D) structures of human protein/protein complexes and the humsavar database of nsSNPs. We analyzed the location of nsSNPS in terms of their location in the protein core, at protein-protein interfaces, and on the surface when not at an interface. Disease-causing nsSNPs that do not occur in the protein core are preferentially located at protein-protein interfaces rather than surface noninterface regions when compared to random segregation. The disruption of the protein-protein interaction can be explained by a range of structural effects including the loss of an electrostatic salt bridge, the destabilization due to reduction of the hydrophobic effect, the formation of a steric clash, and the introduction of a proline altering the main-chain conformation.
许多非同义单核苷酸多态性（nsSNPs）由于蛋白质-蛋白质界面的影响而导致疾病。我们整合了一个人类蛋白质/蛋白质复合物的三维（3D）结构数据库和 nsSNPs 的 humsavar 数据库。我们根据 nsSNPs 在蛋白质核心中的位置、在蛋白质-蛋白质界面上的位置以及不在界面上时的表面位置来分析它们的位置。与随机分离相比，与蛋白质核心中不发生的疾病相关的 nsSNPs 更倾向于位于蛋白质-蛋白质界面而不是表面非界面区域。蛋白质-蛋白质相互作用的破坏可以通过一系列结构效应来解释，包括静电盐桥的丢失、由于疏水性降低导致的不稳定、立体冲突的形成以及脯氨酸的引入改变了主链构象。
