7yn0
Cryo-EM structure of MERS-CoV spike protein, all RBD-down conformation
Structural highlights
FunctionK0BRG7_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 PubMedMost membrane proteins are modified by covalent addition of complex sugars through N- and O-glycosylation. Unlike proteins, glycans do not typically adopt specific secondary structures and remain very mobile, shielding potentially large fractions of protein surface. High glycan conformational freedom hinders complete structural elucidation of glycoproteins. Computer simulations may be used to model glycosylated proteins but require hundreds of thousands of computing hours on supercomputers, thus limiting routine use. Here, we describe GlycoSHIELD, a reductionist method that can be implemented on personal computers to graft realistic ensembles of glycan conformers onto static protein structures in minutes. Using molecular dynamics simulation, small-angle X-ray scattering, cryoelectron microscopy, and mass spectrometry, we show that this open-access toolkit provides enhanced models of glycoprotein structures. Focusing on N-cadherin, human coronavirus spike proteins, and gamma-aminobutyric acid receptors, we show that GlycoSHIELD can shed light on the impact of glycans on the conformation and activity of complex glycoproteins. Rapid simulation of glycoprotein structures by grafting and steric exclusion of glycan conformer libraries.,Tsai YX, Chang NE, Reuter K, Chang HT, Yang TJ, von Bulow S, Sehrawat V, Zerrouki N, Tuffery M, Gecht M, Grothaus IL, Colombi Ciacchi L, Wang YS, Hsu MF, Khoo KH, Hummer G, Hsu SD, Hanus C, Sikora M Cell. 2024 Feb 29;187(5):1296-1311.e26. doi: 10.1016/j.cell.2024.01.034. PMID:38428397[1] From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine. See AlsoReferences
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