Molecular Biophysics Unit, Indian Institute of Science, Bangalore 560012, India.
National Centre for Biological Sciences, TIFR, UAS-GKVK Campus, Bellary road, Bangalore 560065, India; SASTRA Deemed University, Tirumalai Samudram, Thanjavur 613402, India.
Curr Opin Struct Biol. 2017 Jun;44:77-86. doi: 10.1016/j.sbi.2016.12.010. Epub 2017 Jan 11.
Remarkable features that are achieved in a protein-protein complex to precise levels are stability and specificity. Deviation from the normal levels of specificity and stability, which is often caused by mutations, could result in disease conditions. Chemical nature, 3-D arrangement and dynamics of interface residues code for both specificity and stability. This article reviews roles of interfacial residues in transient protein-protein complexes. It is proposed that aside from hotspot residues conferring stability to the complex, a small set of 'rigid' residues at the interface that maintain conformation between complexed and uncomplexed forms, play a major role in conferring specificity. Exceptionally, 'super hotspot' residues, which confer both stability and specificity, are attractive sites for interaction with small molecule inhibitors.
在蛋白质-蛋白质复合物中实现精确水平的显著特征是稳定性和特异性。特异性和稳定性的正常水平的偏差，通常是由突变引起的，可能导致疾病状况。界面残基的化学性质、三维排列和动力学为特异性和稳定性编码。本文综述了界面残基在瞬态蛋白质-蛋白质复合物中的作用。有人提出，除了赋予复合物稳定性的热点残基外，界面上一小部分“刚性”残基在维持复合物和未复合物形式之间的构象方面发挥主要作用，赋予特异性。异常的是，同时赋予稳定性和特异性的“超级热点”残基是与小分子抑制剂相互作用的有吸引力的位点。
