5szs
Glycan shield and epitope masking of a coronavirus spike protein observed by cryo-electron microscopy
Structural highlights
FunctionSPIKE_CVHNL S1 region attaches the virion to the cell membrane by interacting with human ACE2, initiating the infection. Binding to the receptor probably induces conformational changes in the S glycoprotein unmasking the fusion peptide of S2 region and activating membranes fusion. S2 region belongs to the 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) regions 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 (By similarity). Publication Abstract from PubMedThe threat of a major coronavirus pandemic urges the development of strategies to combat these pathogens. Human coronavirus NL63 (HCoV-NL63) is an alpha-coronavirus that can cause severe lower-respiratory-tract infections requiring hospitalization. We report here the 3.4-A-resolution cryo-EM reconstruction of the HCoV-NL63 coronavirus spike glycoprotein trimer, which mediates entry into host cells and is the main target of neutralizing antibodies during infection. The map resolves the extensive glycan shield obstructing the protein surface and, in combination with mass spectrometry, provides a structural framework to understand the accessibility to antibodies. The structure reveals the complete architecture of the fusion machinery including the triggering loop and the C-terminal domains, which contribute to anchoring the trimer to the viral membrane. Our data further suggest that HCoV-NL63 and other coronaviruses use molecular trickery, based on epitope masking with glycans and activating conformational changes, to evade the immune system of infected hosts. Glycan shield and epitope masking of a coronavirus spike protein observed by cryo-electron microscopy.,Walls AC, Tortorici MA, Frenz B, Snijder J, Li W, Rey FA, DiMaio F, Bosch BJ, Veesler D Nat Struct Mol Biol. 2016 Sep 12. doi: 10.1038/nsmb.3293. PMID:27617430[1] From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine. See AlsoReferences
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