first-step mutations for adaptation at elevated temperature increase capsid stability in a virus第一步突变为适应高温增加病毒衣壳的稳定性.pdfVIP

First-Step Mutations for Adaptation at Elevated Temperature Increase Capsid Stability in a Virus Kuo Hao Lee1,5., Craig R. Miller2,3,5., Anna C. Nagel2,5, Holly A. Wichman2,5, Paul Joyce3,4,5, F. Marty Ytreberg1,5* 1 Department of Physics, University of Idaho, Moscow, Idaho, United States of America, 2 Department of Biological Sciences, University of Idaho, Moscow, Idaho, United States of America, 3 Department of Mathematics, University of Idaho, Moscow, Idaho, United States of America, 4 Department of Statistics, University of Idaho, Moscow, Idaho, United States of America, 5 Institute for Bioinformatics and Evolutionary Studies, University of Idaho, Moscow, Idaho, United States of America Abstract 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. Citation: Lee KH, Miller CR, Nagel AC, Wichman HA, Joyce P, et al. (2011) First-Step Mutations for Adaptation at Elevated Temperature Increase Capsid Stability in a Virus. PLoS ONE 6(9): e25640. doi:10.1371/journal.pone.0025640 Editor: Art F. Y. Poon, British Columbia