7R95

Membrane bound structure of HR1 domain of SARS-CoV-2 spike protein

Summary for 7R95

• Entry DOI: 10.2210/pdb7r95/pdb
• NMR Information: BMRB: 30931
• Descriptor: Spike protein S2 (1 entity in total)
• Functional Keywords: sars-cov-2, heptad repeat, residual dipolar couplings, bicelles, lipid-water interface, viral protein
• Biological source: Severe acute respiratory syndrome coronavirus 2 (2019-nCoV, SARS-CoV-2)
• Total number of polymer chains: 1
• Total formula weight: 5928.65

Authors

Chiliveri, S.C.,Bax, A. (deposition date: 2021-06-28, release date: 2021-10-20, Last modification date: 2024-05-15)

Primary citation

Chiliveri, S.C.,Louis, J.M.,Ghirlando, R.,Bax, A.
Transient lipid-bound states of spike protein heptad repeats provide insights into SARS-CoV-2 membrane fusion.
Sci Adv, 7:eabk2226-eabk2226, 2021

PubMed Abstract: Entry of SARS-CoV-2 into a host cell is mediated by spike, a class I viral fusion protein responsible for merging the viral and host cell membranes. Recent studies have revealed atomic-resolution models for both the postfusion 6-helix bundle (6HB) and the prefusion state of spike. However, a mechanistic understanding of the molecular basis for the intervening structural transition, important for the design of fusion inhibitors, has remained elusive. Using nuclear magnetic resonance spectroscopy and other biophysical methods, we demonstrate the presence of α-helical, membrane-bound, intermediate states of spike’s heptad repeat (HR1 and HR2) domains that are embedded at the lipid-water interface while in a slow dynamic equilibrium with the postfusion 6HB state. These results support a model where the HR domains lower the large energy barrier associated with membrane fusion by destabilizing the host and viral membranes, while 6HB formation actively drives their fusion by forcing physical proximity.

PubMed: 34623907
DOI: 10.1126/sciadv.abk2226

Experimental method

SOLUTION NMR