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Cryo-electron microscopy structure of a coronavirus spike glycoprotein trimerCryo-electron microscopy structure of a coronavirus spike glycoprotein trimer
Structural highlights
FunctionSPIKE_CVMA5 S1 attaches the virion to the cell membrane by interacting with murine CEACAM1, initiating the infection.[1] S2 is a class I viral fusion protein. Under the current model, the protein has at least 3 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 plasma cell membranes. Presumably interacts with target cell lipid raft after cell attachment.[2] Publication Abstract from PubMedThe tremendous pandemic potential of coronaviruses was demonstrated twice in the past few decades by two global outbreaks of deadly pneumonia. Entry of coronaviruses into cells is mediated by the transmembrane spike glycoprotein S, which forms a trimer carrying receptor-binding and membrane fusion functions. S also contains the principal antigenic determinants and is the target of neutralizing antibodies. Here we present the structure of a mouse coronavirus S trimer ectodomain determined at 4.0 A resolution by single particle cryo-electron microscopy. It reveals the metastable pre-fusion architecture of S and highlights key interactions stabilizing it. The structure shares a common core with paramyxovirus F proteins, implicating mechanistic similarities and an evolutionary connection between these viral fusion proteins. The accessibility of the highly conserved fusion peptide at the periphery of the trimer indicates potential vaccinology strategies to elicit broadly neutralizing antibodies against coronaviruses. Finally, comparison with crystal structures of human coronavirus S domains allows rationalization of the molecular basis for species specificity based on the use of spatially contiguous but distinct domains. Cryo-electron microscopy structure of a coronavirus spike glycoprotein trimer.,Walls AC, Tortorici MA, Bosch BJ, Frenz B, Rottier PJ, DiMaio F, Rey FA, Veesler D Nature. 2016 Feb 8. doi: 10.1038/nature16988. PMID:26855426[3] From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine. See AlsoReferences
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