Department of Physics, University of Idaho, Moscow, Idaho, United States of America.
PLoS One. 2011;6(9):e25640. doi: 10.1371/journal.pone.0025640. Epub 2011 Sep 29.
The relationship between mutation, protein stability and protein function plays a central role in molecular evolution. Mutations tend to be destabilizing, including those that would confer novel functions such as host-switching or antibiotic resistance. Elevated temperature may play an important role in preadapting a protein for such novel functions by selecting for stabilizing mutations. In this study, we test the stability change conferred by single mutations that arise in a G4-like bacteriophage adapting to elevated temperature. The vast majority of these mutations map to interfaces between viral coat proteins, suggesting they affect protein-protein interactions. We assess their effects by estimating thermodynamic stability using molecular dynamic simulations and measuring kinetic stability using experimental decay assays. The results indicate that most, though not all, of the observed mutations are stabilizing.
突变、蛋白质稳定性和蛋白质功能之间的关系在分子进化中起着核心作用。突变往往会使蛋白质变得不稳定，包括那些赋予新功能的突变，如宿主转换或抗生素耐药性。高温可能通过选择稳定突变，在蛋白质适应新功能方面发挥重要作用。在这项研究中，我们测试了在适应高温的 G4 样噬菌体中出现的单突变所带来的稳定性变化。这些突变绝大多数都发生在病毒外壳蛋白之间的界面上，这表明它们影响了蛋白质-蛋白质相互作用。我们通过使用分子动力学模拟来估计热力学稳定性，并通过实验衰变测定来测量动力学稳定性，从而评估这些突变的影响。结果表明，大多数（尽管不是全部）观察到的突变是稳定的。
