7s3m
From Proteopedia
MERS-CoV S stem helix peptide bound to Fab22
Structural highlights
FunctionSPIKE_MERS1 Attaches the virion to the cell membrane by interacting with host receptor, initiating the infection (By similarity). Interacts with host DPP4 to mediate virla entry.[HAMAP-Rule:MF_04099][1] 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] Acts as a viral fusion peptide which is unmasked following S2 cleavage occurring upon virus endocytosis.[HAMAP-Rule:MF_04099] Publication Abstract from PubMedCurrent coronavirus (CoV) vaccines primarily target immunodominant epitopes in the S1 subunit, which are poorly conserved and susceptible to escape mutations, thus threatening vaccine efficacy. Here, we use structure-guided protein engineering to remove the S1 subunit from the Middle East respiratory syndrome (MERS)-CoV spike (S) glycoprotein and develop stabilized stem (SS) antigens. Vaccination with MERS SS elicits cross-reactive beta-CoV antibody responses and protects mice against lethal MERS-CoV challenge. High-throughput screening of antibody-secreting cells from MERS SS-immunized mice led to the discovery of a panel of cross-reactive monoclonal antibodies. Among them, antibody IgG22 binds with high affinity to both MERS-CoV and severe acute respiratory syndrome (SARS)-CoV-2 S proteins, and a combination of electron microscopy and crystal structures localizes the epitope to a conserved coiled-coil region in the S2 subunit. Passive transfer of IgG22 protects mice against both MERS-CoV and SARS-CoV-2 challenge. Collectively, these results provide a proof of principle for cross-reactive CoV antibodies and inform the development of pan-CoV vaccines and therapeutic antibodies. Stabilized coronavirus spike stem elicits a broadly protective antibody.,Hsieh CL, Werner AP, Leist SR, Stevens LJ, Falconer E, Goldsmith JA, Chou CW, Abiona OM, West A, Westendorf K, Muthuraman K, Fritch EJ, Dinnon KH 3rd, Schafer A, Denison MR, Chappell JD, Baric RS, Graham BS, Corbett KS, McLellan JS Cell Rep. 2021 Nov 2;37(5):109929. doi: 10.1016/j.celrep.2021.109929. Epub 2021 , Oct 16. PMID:34710354[2] From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine. See AlsoReferences
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