Structural highlights
Function
K0BRG7_MERS 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 PubMed
The Middle East respiratory syndrome coronavirus (MERS-CoV) causes severe and often lethal respiratory illness in humans, and no vaccines or specific treatments are available. Infections are initiated via binding of the MERS-CoV spike (S) glycoprotein to sialosides and dipeptidyl-peptidase 4 (the attachment and entry receptors, respectively). To understand MERS-CoV engagement of sialylated receptors, we determined the cryo-EM structures of S in complex with 5-N-acetyl neuraminic acid, 5-N-glycolyl neuraminic acid, sialyl-Lewis(X), alpha2,3-sialyl-N-acetyl-lactosamine and alpha2,6-sialyl-N-acetyl-lactosamine at 2.7-3.0 A resolution. We show that recognition occurs via a conserved groove that is essential for MERS-CoV S-mediated attachment to sialosides and entry into human airway epithelial cells. Our data illuminate MERS-CoV S sialoside specificity and suggest that selectivity for alpha2,3-linked over alpha2,6-linked receptors results from enhanced interactions with the former class of oligosaccharides. This study provides a structural framework explaining MERS-CoV attachment to sialoside receptors and identifies a site of potential vulnerability to inhibitors of viral entry.
Structures of MERS-CoV spike glycoprotein in complex with sialoside attachment receptors.,Park YJ, Walls AC, Wang Z, Sauer MM, Li W, Tortorici MA, Bosch BJ, DiMaio F, Veesler D Nat Struct Mol Biol. 2019 Dec;26(12):1151-1157. doi: 10.1038/s41594-019-0334-7., Epub 2019 Dec 2. PMID:31792450[1]
From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine.
See Also
References
- ↑ Park YJ, Walls AC, Wang Z, Sauer MM, Li W, Tortorici MA, Bosch BJ, DiMaio F, Veesler D. Structures of MERS-CoV spike glycoprotein in complex with sialoside attachment receptors. Nat Struct Mol Biol. 2019 Dec;26(12):1151-1157. doi: 10.1038/s41594-019-0334-7., Epub 2019 Dec 2. PMID:31792450 doi:http://dx.doi.org/10.1038/s41594-019-0334-7
