7JJC

Crystal structure of neuropilin-1 b1 domain in complex with SARS-CoV-2 S1 C-end rule (CendR) peptide

Summary for 7JJC

• Entry DOI: 10.2210/pdb7jjc/pdb
• Descriptor: Neuropilin-1, Spike protein S1, DI(HYDROXYETHYL)ETHER, ... (5 entities in total)
• Functional Keywords: neuropilin-1, receptor binding, coronavirus, sars-cov-2, spike protein, signaling protein
• Biological source: Homo sapiens (Human); More
• Total number of polymer chains: 8
• Total formula weight: 79201.25

Authors

Chen, K.-E.,Collins, B.M. (deposition date: 2020-07-25, release date: 2020-10-28, Last modification date: 2024-10-09)

Primary citation

Daly, J.L.,Simonetti, B.,Klein, K.,Chen, K.E.,Williamson, M.K.,Anton-Plagaro, C.,Shoemark, D.K.,Simon-Gracia, L.,Bauer, M.,Hollandi, R.,Greber, U.F.,Horvath, P.,Sessions, R.B.,Helenius, A.,Hiscox, J.A.,Teesalu, T.,Matthews, D.A.,Davidson, A.D.,Collins, B.M.,Cullen, P.J.,Yamauchi, Y.
Neuropilin-1 is a host factor for SARS-CoV-2 infection.
Science, 370:861-865, 2020

PubMed Abstract: Severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2), the causative agent of coronavirus disease 2019 (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 carboxyl-terminal sequence on S1, which conforms to a C-end rule (CendR) motif that binds to cell surface neuropilin-1 (NRP1) and NRP2 receptors. We used x-ray crystallography and biochemical approaches to show that the S1 CendR motif directly bound NRP1. Blocking this interaction by RNA interference 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.

PubMed: 33082294
DOI: 10.1126/science.abd3072

Experimental method

X-RAY DIFFRACTION (2.36 Å)