7vq0
From Proteopedia
Cryo-EM structure of the SARS-CoV-2 spike protein (2-up RBD) bound to neutralizing nanobodies P86
Structural highlights
FunctionSPIKE_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][1] [2] [3] 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 PubMedWe are amid the historic coronavirus infectious disease 2019 (COVID-19) pandemic. Imbalances in the accessibility of vaccines, medicines, and diagnostics among countries, regions, and populations, and those in war crises, have been problematic. Nanobodies are small, stable, customizable, and inexpensive to produce. Herein, we present a panel of nanobodies that can detect the spike proteins of five SARS-CoV-2 variants of concern (VOCs) including Omicron. Here we show via ELISA, lateral flow, kinetic, flow cytometric, microscopy, and Western blotting assays that our nanobodies can quantify the spike variants. This panel of nanobodies broadly neutralizes viral infection caused by pseudotyped and authentic SARS-CoV-2 VOCs. Structural analyses show that the P86 clone targets epitopes that are conserved yet unclassified on the receptor-binding domain (RBD) and contacts the N-terminal domain (NTD). Human antibodies rarely access both regions; consequently, the clone buries hidden crevasses of SARS-CoV-2 spike proteins that go undetected by conventional antibodies. A panel of nanobodies recognizing conserved hidden clefts of all SARS-CoV-2 spike variants including Omicron.,Maeda R, Fujita J, Konishi Y, Kazuma Y, Yamazaki H, Anzai I, Watanabe T, Yamaguchi K, Kasai K, Nagata K, Yamaoka Y, Miyakawa K, Ryo A, Shirakawa K, Sato K, Makino F, Matsuura Y, Inoue T, Imura A, Namba K, Takaori-Kondo A Commun Biol. 2022 Jul 6;5(1):669. doi: 10.1038/s42003-022-03630-3. PMID:35794202[4] From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine. See AlsoReferences
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Categories: Large Structures | Severe acute respiratory syndrome coronavirus 2 | Vicugna pacos | Anzai I | Fujita J | Imura A | Inoue T | Kasai K | Kazuma Y | Konishi Y | Maeda R | Makino F | Matsuura Y | Miyakawa K | Nagata K | Namba K | Ryo A | Shirakawa K | Takaori-Kondo A | Yamaguchi K | Yamaoka Y | Yamazaki H
