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.
全体 : Ectodomain of spike glycoprotein from SARS-CoV-2 expressed in HEK...
全体
名称: Ectodomain of spike glycoprotein from SARS-CoV-2 expressed in HEK cells and purified. Data were collected in the presence of excess biliverdin.
要素
複合体: Ectodomain of spike glycoprotein from SARS-CoV-2 expressed in HEK cells and purified. Data were collected in the presence of excess biliverdin.
タンパク質・ペプチド: Spike glycoprotein
リガンド: BILIVERDINE IX ALPHA
リガンド: 2-acetamido-2-deoxy-beta-D-glucopyranose
リガンド: water
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超分子 #1: Ectodomain of spike glycoprotein from SARS-CoV-2 expressed in HEK...
超分子
名称: Ectodomain of spike glycoprotein from SARS-CoV-2 expressed in HEK cells and purified. Data were collected in the presence of excess biliverdin. タイプ: complex / ID: 1 / 親要素: 0 / 含まれる分子: #1
由来(天然)
生物種: Severe acute respiratory syndrome coronavirus 2 (ウイルス)
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
0.6 mg/ml final concentration in TBSE supplemented with 0.1% n-octylglucoside) with 25 micro M biliverdin
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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: FEI FALCON III (4k x 4k) 検出モード: COUNTING / 撮影したグリッド数: 1 / 実像数: 15962 / 平均電子線量: 33.0 e/Å2 詳細: A total of 15962 movies were recorded with a calibrated pixel size of 1.09 Angstrom and a total electron exposure of 33 electrons per square Angstrom, spread over 30 frames in single electron counting mode.