7NTC

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

7NTC の概要

• エントリーDOI: 10.2210/pdb7ntc/pdb
• EMDBエントリー: 12587
• 分子名称: Spike glycoprotein, P008_056 Fab Heavy chain, P008_056 Fab Light chain, ... (6 entities in total)
• 機能のキーワード: sars-cov-2, spike, biliverdin, covid19, antibody, fab, epitope, ntd, viral protein
• 由来する生物種: Severe acute respiratory syndrome coronavirus 2 (2019-nCoV); 詳細
• タンパク質・核酸の鎖数: 5
• 化学式量合計: 497492.51

構造登録者

Rosa, A.,Pye, V.E.,Nans, A.,Cherepanov, P. (登録日: 2021-03-09, 公開日: 2021-04-28, 最終更新日: 2024-10-23)

主引用文献

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

実験手法

ELECTRON MICROSCOPY (3.6 Å)