7qur

SARS-CoV-2 Spike with ethylbenzamide-tri-iodo Siallyllactose, C3 symmetry

spinqualitylabelsall models 7qur, resolution 2.27Å Show:Asymmetric Unit Biological Assembly Drag the structure with the mouse to rotate   Export Animated Image   Print3D Structural highlights 7qur is a 3 chain structure with sequence from Escherichia virus T4 and Severe acute respiratory syndrome coronavirus 2. Full crystallographic information is available from OCA. For a guided tour on the structure components use FirstGlance. Method: Electron Microscopy, Resolution 2.27Å Ligands: EIC, FUC, GE9, NAG, SIA Resources: FirstGlance, OCA, PDBe, RCSB, PDBsum, ProSAT Function SPIKE_SARS2 attaches the virion to the cell membrane by interacting with host receptor, initiating the infection (By similarity). Binding to human ACE2 receptor and internalization of the virus into the endosomes of the host cell induces conformational changes in the Spike glycoprotein (PubMed:32142651, PubMed:32075877, PubMed:32155444). Uses also human TMPRSS2 for priming in human lung cells which is an essential step for viral entry (PubMed:32142651). Proteolysis by cathepsin CTSL may unmask the fusion peptide of S2 and activate membranes fusion within endosomes.[HAMAP-Rule:MF_04099] 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 PubMed Many pathogens exploit host cell-surface glycans. However, precise analyses of glycan ligands binding with heavily modified pathogen proteins can be confounded by overlapping sugar signals and/or compounded with known experimental constraints. Universal saturation transfer analysis (uSTA) builds on existing nuclear magnetic resonance spectroscopy to provide an automated workflow for quantitating protein-ligand interactions. uSTA reveals that early-pandemic, B-origin-lineage severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) spike trimer binds sialoside sugars in an "end-on" manner. uSTA-guided modeling and a high-resolution cryo-electron microscopy structure implicate the spike N-terminal domain (NTD) and confirm end-on binding. This finding rationalizes the effect of NTD mutations that abolish sugar binding in SARS-CoV-2 variants of concern. Together with genetic variance analyses in early pandemic patient cohorts, this binding implicates a sialylated polylactosamine motif found on tetraantennary N-linked glycoproteins deep in the human lung as potentially relevant to virulence and/or zoonosis. Pathogen-sugar interactions revealed by universal saturation transfer analysis.,Buchanan CJ, Gaunt B, Harrison PJ, Yang Y, Liu J, Khan A, Giltrap AM, Le Bas A, Ward PN, Gupta K, Dumoux M, Tan TK, Schimaski L, Daga S, Picchiotti N, Baldassarri M, Benetti E, Fallerini C, Fava F, Giliberti A, Koukos PI, Davy MJ, Lakshminarayanan A, Xue X, Papadakis G, Deimel LP, Casablancas-Antras V, Claridge TDW, Bonvin AMJJ, Sattentau QJ, Furini S, Gori M, Huo J, Owens RJ, Schaffitzel C, Berger I, Renieri A, Naismith JH, Baldwin AJ, Davis BG Science. 2022 Jul 22;377(6604):eabm3125. doi: 10.1126/science.abm3125. Epub 2022 , Jul 22. PMID:35737812 From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine.

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