6YM0
Crystal structure of the SARS-CoV-2 receptor binding domain in complex with CR3022 Fab (crystal form 1)
Summary for 6YM0
| Entry DOI | 10.2210/pdb6ym0/pdb |
| Related | 6YLA |
| Descriptor | Spike glycoprotein, heavy chain, light chain (3 entities in total) |
| Functional Keywords | sars-cov-2, receptor binding domain (rbd), cr3022, vagabond, viral protein |
| Biological source | Severe acute respiratory syndrome coronavirus 2 (2019-nCoV) More |
| Total number of polymer chains | 3 |
| Total formula weight | 72648.15 |
| Authors | Huo, J.,Zhao, Y.,Ren, J.,Zhou, D.,Ginn, H.M.,Fry, E.E.,Owens, R.,Stuart, D.I. (deposition date: 2020-04-07, release date: 2020-04-29, Last modification date: 2024-10-23) |
| 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 Cited by 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: 32585135DOI: 10.1016/j.chom.2020.06.010 PDB entries with the same primary citation |
| Experimental method | X-RAY DIFFRACTION (4.36 Å) |
Structure validation
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