6Z97

Structure of the prefusion SARS-CoV-2 spike glycoprotein

Summary for 6Z97

• Entry DOI: 10.2210/pdb6z97/pdb
• Related: 6YLA 6YM0 6YOR
• EMDB information: 11119
• Descriptor: Spike glycoprotein,Fibritin, 2-acetamido-2-deoxy-beta-D-glucopyranose-(1-4)-2-acetamido-2-deoxy-beta-D-glucopyranose, 2-acetamido-2-deoxy-beta-D-glucopyranose (3 entities in total)
• Functional Keywords: sars-cov-2 spike glycoprotein, rbd, cr3022, complex, viral protein
• Biological source: Severe acute respiratory syndrome coronavirus 2 (2019-nCoV); More
• Total number of polymer chains: 3
• Total formula weight: 437839.15

Authors

Duyvesteyn, H.M.E.,Ren, J.,Zhao, Y.,Zhou, D.,Huo, J.,Carrique, L.,Malinauskas, T.,Ruza, R.R.,Shah, P.N.M.,Fry, E.E.,Owens, R.,Stuart, D.I. (deposition date: 2020-06-03, release date: 2020-07-01, Last modification date: 2024-11-13)

Primary citation

Huo, J.,Zhao, Y.,Ren, J.,Zhou, D.,Duyvesteyn, H.M.E.,Ginn, H.M.,Carrique, L.,Malinauskas, T.,Ruza, R.R.,Shah, P.N.M.,Tan, T.K.,Rijal, P.,Coombes, N.,Bewley, K.R.,Tree, J.A.,Radecke, J.,Paterson, N.G.,Supasa, P.,Mongkolsapaya, J.,Screaton, G.R.,Carroll, M.,Townsend, A.,Fry, E.E.,Owens, R.J.,Stuart, D.I.
Neutralization of SARS-CoV-2 by Destruction of the Prefusion Spike.
Cell Host Microbe, 28:445-454.e6, 2020

PubMed Abstract: There are as yet no licensed therapeutics for the COVID-19 pandemic. The causal coronavirus (SARS-CoV-2) binds host cells via a trimeric spike whose receptor binding domain (RBD) recognizes angiotensin-converting enzyme 2, initiating conformational changes that drive membrane fusion. We find that the monoclonal antibody CR3022 binds the RBD tightly, neutralizing SARS-CoV-2, and report the crystal structure at 2.4 Å of the Fab/RBD complex. Some crystals are suitable for screening for entry-blocking inhibitors. The highly conserved, structure-stabilizing CR3022 epitope is inaccessible in the prefusion spike, suggesting that CR3022 binding facilitates conversion to the fusion-incompetent post-fusion state. Cryogenic electron microscopy (cryo-EM) analysis confirms that incubation of spike with CR3022 Fab leads to destruction of the prefusion trimer. Presentation of this cryptic epitope in an RBD-based vaccine might advantageously focus immune responses. Binders at this epitope could be useful therapeutically, possibly in synergy with an antibody that blocks receptor attachment.

PubMed: 32585135
DOI: 10.1016/j.chom.2020.06.010

Experimental method

ELECTRON MICROSCOPY (3.4 Å)