近日,美国华盛顿大学Jesse D. Bloom及其研究组通过对SARS-CoV-2受体结合结构域的深度突变筛选,揭示出蛋白折叠和ACE2结合的限制区域。2020年8月11日,《细胞》杂志在线发表了这项成果。
Title: Deep mutational scanning of SARS-CoV-2 receptor binding domain reveals constraints on folding and ACE2 binding
Author: Tyler N. Starr, Allison J. Greaney, Sarah K. Hilton, Daniel Ellis, Katharine H.D. Crawford, Adam S. Dingens, Mary Jane Navarro, John E. Bowen, M. Alejandra Tortorici, Alexandra C. Walls, Neil P. King, David Veesler, Jesse D. Bloom
Issue&Volume: 2020-08-11
Abstract: The receptor binding domain (RBD) of the SARS-CoV-2 spike glycoprotein mediates viral attachment to ACE2 receptor, and is a major determinant of host range and a dominant target of neutralizing antibodies. Here we experimentally measure how all amino-acid mutations to the RBD affect expression of folded protein and its affinity for ACE2. Most mutations are deleterious for RBD expression and ACE2 binding, and we identify constrained regions on the RBD’s surface that may be desirable targets for vaccines and antibody-based therapeutics. But a substantial number of mutations are well tolerated or even enhance ACE2 binding, including at ACE2 interface residues that vary across SARS-related coronaviruses. However, we find no evidence that these ACE2-affinity enhancing mutations have been selected in current SARS-CoV-2 pandemic isolates. We present an interactive visualization and open analysis pipeline to facilitate use of our dataset for vaccine design and functional annotation of mutations observed during viral surveillance.
DOI: 10.1016/j.cell.2020.08.012
Source: https://www.cell.com/cell/fulltext/S0092-8674(20)31003-5