Michael Smith Laboratories, University of British Columbia, Vancouver, V6T 1Z4, BC, Canada.
Michael Smith Laboratories, University of British Columbia, Vancouver, V6T 1Z4, BC, Canada.
Curr Opin Struct Biol. 2021 Aug;69:160-168. doi: 10.1016/j.sbi.2021.04.007. Epub 2021 May 30.
Proteins are molecular machines composed of complex, highly connected amino acid networks. Their functional optimization requires the reorganization of these intramolecular networks by evolution. In this review, we discuss the mechanisms by which epistasis, that is, the dependence of the effect of a mutation on the genetic background, rewires intramolecular interactions to alter protein function. Deciphering the biophysical basis of epistasis is crucial to our understanding of evolutionary dynamics and the elucidation of sequence-structure-function relationships. We featured recent studies that provide insights into the molecular mechanisms giving rise to epistasis, particularly at the structural level. These studies illustrate the convoluted and fascinating nature of the intramolecular networks co-opted by epistasis during the evolution of protein function.
蛋白质是由复杂的、高度连接的氨基酸网络组成的分子机器。它们的功能优化需要进化来重新组织这些分子内网络。在这篇综述中，我们讨论了上位性（即突变的效应依赖于遗传背景）改变蛋白质功能的机制，即通过改变分子内相互作用来重新布线。解析上位性的生物物理基础对于我们理解进化动态和阐明序列-结构-功能关系至关重要。我们重点介绍了一些最近的研究，这些研究提供了对导致上位性的分子机制的深入了解，特别是在结构水平上。这些研究说明了在蛋白质功能进化过程中，上位性所涉及的分子内网络的复杂和迷人性质。
