7xsw
From Proteopedia
Structure of SARS-CoV-2 antibody S309 with GX/P2V/2017 RBD
Structural highlights
FunctionA0A6G9KP06_9BETC Spike protein S1: attaches the virion to the cell membrane by interacting with host receptor, initiating the infection.[HAMAP-Rule:MF_04099] Spike protein S2': Acts as a viral fusion peptide which is unmasked following S2 cleavage occurring upon virus endocytosis.[HAMAP-Rule:MF_04099] Spike protein S2: mediates fusion of the virion and cellular membranes by acting as a class I viral fusion protein. Under the current model, the protein has at least three conformational states: pre-fusion native state, pre-hairpin intermediate state, and post-fusion hairpin state. During viral and target cell membrane fusion, the coiled coil regions (heptad repeats) assume a trimer-of-hairpins structure, positioning the fusion peptide in close proximity to the C-terminal region of the ectodomain. The formation of this structure appears to drive apposition and subsequent fusion of viral and target cell membranes.[HAMAP-Rule:MF_04099] Publication Abstract from PubMedSince the identification of severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2), the etiological agent of COVID-19, multiple SARS-CoV-2-related viruses have been characterized, including pangolin-origin GD/1/2019 and GX/P2V/2017. Our previous study indicated that both viruses have the potential to infect humans. Here, we find that CB6 (commercial name etesevimab), a COVID-19 therapeutic monoclonal antibody (MAb) developed by our group, efficiently inhibits GD/1/2019 but not GX/P2V/2017. A total of 50 SARS-CoV-2 MAbs divided into seven groups based on their receptor-binding domain (RBD) epitopes, together with the COVID-19 convalescent sera, are systematically screened for their cross-binding and cross-neutralizing properties against GX/P2V/2017. We find that GX/P2V/2017 displays substantial immune difference from SARS-CoV-2. Furthermore, we solve two complex structures of the GX/P2V/2017 RBD with MAbs belonging to RBD-1 and RBD-5, providing a structural basis for their different antigenicity. These results highlight the necessity for broad anti-coronavirus countermeasures and shed light on potential therapeutic targets. Cross-reaction of current available SARS-CoV-2 MAbs against the pangolin-origin coronavirus GX/P2V/2017.,Jia Y, Niu S, Hu Y, Chai Y, Zheng A, Su C, Wu L, Han P, Han P, Lu D, Liu Z, Yan X, Tian D, Chen Z, Qi J, Tian WX, Wang Q, Gao GF Cell Rep. 2022 Dec 13;41(11):111831. doi: 10.1016/j.celrep.2022.111831. Epub 2022 , Nov 29. PMID:36493785[1] From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine. See AlsoReferences
| ||||||||||||||||||||
