7jjc
From Proteopedia
Crystal structure of neuropilin-1 b1 domain in complex with SARS-CoV-2 S1 C-end rule (CendR) peptide
Structural highlights
FunctionNRP1_HUMAN The membrane-bound isoform 1 is a receptor involved in the development of the cardiovascular system, in angiogenesis, in the formation of certain neuronal circuits and in organogenesis outside the nervous system. It mediates the chemorepulsant activity of semaphorins. It binds to semaphorin 3A, The PLGF-2 isoform of PGF, The VEGF-165 isoform of VEGF and VEGF-B. Coexpression with KDR results in increased VEGF-165 binding to KDR as well as increased chemotaxis. It may regulate VEGF-induced angiogenesis. The soluble isoform 2 binds VEGF-165 and appears to inhibit its binding to cells. It may also induce apoptosis by sequestering VEGF-165. May bind as well various members of the semaphorin family. Its expression has an averse effect on blood vessel number and integrity. Publication Abstract from PubMedSARS-CoV-2, the causative agent of COVID-19, uses the viral Spike (S) protein for host cell attachment and entry. The host protease furin cleaves the full-length precursor S glycoprotein into two associated polypeptides: S1 and S2. Cleavage of S generates a polybasic Arg-Arg-Ala-Arg C-terminal sequence on S1, which conforms to a C-end rule (CendR) motif that binds to cell surface Neuropilin-1 (NRP1) and Neuropilin-2 (NRP2) receptors. Here, we used X-ray crystallography and biochemical approaches to show that the S1 CendR motif directly bound NRP1. Blocking this interaction using RNAi or selective inhibitors reduced SARS-CoV-2 entry and infectivity in cell culture. NRP1 thus serves as a host factor for SARS-CoV-2 infection and may potentially provide a therapeutic target for COVID-19. Neuropilin-1 is a host factor for SARS-CoV-2 infection.,Daly JL, Simonetti B, Klein K, Chen KE, Williamson MK, Anton-Plagaro C, Shoemark DK, Simon-Gracia L, Bauer M, Hollandi R, Greber UF, Horvath P, Sessions RB, Helenius A, Hiscox JA, Teesalu T, Matthews DA, Davidson AD, Collins BM, Cullen PJ, Yamauchi Y Science. 2020 Oct 20. pii: science.abd3072. doi: 10.1126/science.abd3072. PMID:33082294[1] From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine. See AlsoReferences
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