7NTC

Trimeric SARS-CoV-2 spike ectodomain bound to P008_056 Fab

Summary for 7NTC

• Entry DOI: 10.2210/pdb7ntc/pdb
• EMDB information: 12587
• Descriptor: Spike glycoprotein, P008_056 Fab Heavy chain, P008_056 Fab Light chain, ... (6 entities in total)
• Functional Keywords: sars-cov-2, spike, biliverdin, covid19, antibody, fab, epitope, ntd, viral protein
• Biological source: Severe acute respiratory syndrome coronavirus 2 (2019-nCoV); More
• Total number of polymer chains: 5
• Total formula weight: 497492.51

Authors

Rosa, A.,Pye, V.E.,Nans, A.,Cherepanov, P. (deposition date: 2021-03-09, release date: 2021-04-28, Last modification date: 2024-10-23)

Primary citation

Rosa, A.,Pye, V.E.,Graham, C.,Muir, L.,Seow, J.,Ng, K.W.,Cook, N.J.,Rees-Spear, C.,Parker, E.,Dos Santos, M.S.,Rosadas, C.,Susana, A.,Rhys, H.,Nans, A.,Masino, L.,Roustan, C.,Christodoulou, E.,Ulferts, R.,Wrobel, A.G.,Short, C.E.,Fertleman, M.,Sanders, R.W.,Heaney, J.,Spyer, M.,Kjaer, S.,Riddell, A.,Malim, M.H.,Beale, R.,MacRae, J.I.,Taylor, G.P.,Nastouli, E.,van Gils, M.J.,Rosenthal, P.B.,Pizzato, M.,McClure, M.O.,Tedder, R.S.,Kassiotis, G.,McCoy, L.E.,Doores, K.J.,Cherepanov, P.
SARS-CoV-2 can recruit a heme metabolite to evade antibody immunity.
Sci Adv, 7:-, 2021

PubMed Abstract: The coronaviral spike is the dominant viral antigen and the target of neutralizing antibodies. We show that SARS-CoV-2 spike binds biliverdin and bilirubin, the tetrapyrrole products of heme metabolism, with nanomolar affinity. Using cryo-electron microscopy and x-ray crystallography, we mapped the tetrapyrrole interaction pocket to a deep cleft on the spike N-terminal domain (NTD). At physiological concentrations, biliverdin significantly dampened the reactivity of SARS-CoV-2 spike with immune sera and inhibited a subset of neutralizing antibodies. Access to the tetrapyrrole-sensitive epitope is gated by a flexible loop on the distal face of the NTD. Accompanied by profound conformational changes in the NTD, antibody binding requires relocation of the gating loop, which folds into the cleft vacated by the metabolite. Our results indicate that SARS-CoV-2 spike NTD harbors a dominant epitope, access to which can be controlled by an allosteric mechanism that is regulated through recruitment of a metabolite.

PubMed: 33888467
DOI: 10.1126/sciadv.abg7607

Experimental method

ELECTRON MICROSCOPY (3.6 Å)