6zlr
From Proteopedia
Soaking competent crystal form of the SARS-CoV-2 Receptor Binding Domain (RBD):CR3022 complex.
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 PubMedIn-crystal fragment screening is a powerful tool to chemically probe the surfaces used by proteins to interact, and identify the chemical space worth exploring to design protein-protein inhibitors. A crucial prerequisite is the identification of a crystal form where the target area is exposed and accessible to be probed by fragments. Here we report a crystal form of the SARS-CoV-2 Receptor Binding Domain in complex with the CR3022 antibody where the ACE2 binding site on the Receptor Binding Domain is exposed and accessible. This crystal form of the complex is a valuable tool to develop antiviral molecules that could act by blocking the virus entry in cells. A New Crystal Form of the SARS-CoV-2 Receptor Binding Domain: CR3022 Complex-An Ideal Target for In-Crystal Fragment Screening of the ACE2 Binding Site Surface.,Nichols C, Ng J, Keshu A, Fraternali F, De Nicola GF Front Pharmacol. 2020 Dec 14;11:615211. doi: 10.3389/fphar.2020.615211. , eCollection 2020. PMID:33381049[4] From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine. See AlsoReferences
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