ジャーナル: Sci Adv / 年: 2021 タイトル: SARS-CoV-2 can recruit a heme metabolite to evade antibody immunity. 著者: Annachiara Rosa / Valerie E Pye / Carl Graham / Luke Muir / Jeffrey Seow / Kevin W Ng / Nicola J Cook / Chloe Rees-Spear / Eleanor Parker / Mariana Silva Dos Santos / Carolina Rosadas / ...著者: Annachiara Rosa / Valerie E Pye / Carl Graham / Luke Muir / Jeffrey Seow / Kevin W Ng / Nicola J Cook / Chloe Rees-Spear / Eleanor Parker / Mariana Silva Dos Santos / Carolina Rosadas / Alberto Susana / Hefin Rhys / Andrea Nans / Laura Masino / Chloe Roustan / Evangelos Christodoulou / Rachel Ulferts / Antoni G Wrobel / Charlotte-Eve Short / Michael Fertleman / Rogier W Sanders / Judith Heaney / Moira Spyer / Svend Kjær / Andy Riddell / Michael H Malim / Rupert Beale / James I MacRae / Graham P Taylor / Eleni Nastouli / Marit J van Gils / Peter B Rosenthal / Massimo Pizzato / Myra O McClure / Richard S Tedder / George Kassiotis / Laura E McCoy / Katie J Doores / Peter Cherepanov / 要旨: 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 ...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.
超分子 #1: Stabilised SARS-CoV-2 spike ectodomain trimer bound to one P008_0...
超分子
名称: Stabilised SARS-CoV-2 spike ectodomain trimer bound to one P008_056 Fab タイプ: complex / ID: 1 / 親要素: 0 / 含まれる分子: #1-#3 詳細: natural source below: Spike is SARS-Cov-2 and Fab is Human - there is only option for one natural source below!
pH: 8 詳細: 150 mM NaCl, 1 mM ethylenediaminetetraacetic acid (EDTA), 25 mM Tris-HCl, pH 8.0
グリッド
モデル: Quantifoil R2/2 / 前処理 - タイプ: GLOW DISCHARGE
凍結
凍結剤: ETHANE
詳細
SARS-CoV-2 spike ectodomain (0.6 mg/ml final concentration in TBSE supplemented with 0.1% n-octylglucoside) with 0.2 mg/ml P008_056 Fab
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電子顕微鏡法
顕微鏡
FEI TITAN KRIOS
撮影
フィルム・検出器のモデル: GATAN K2 QUANTUM (4k x 4k) 検出モード: COUNTING / 撮影したグリッド数: 1 / 実像数: 17010 / 平均電子線量: 51.0 e/Å2 詳細: A total of 17010 movies were collected with a pixel size of 1.38 Angstrom and total electron exposure of 51 electrons per square Angstrom, spread over 40 frames.