EMDB/PDB/SASBDBから引用されている文献のデータベース

キーワード
構造解析手法	All X線回折 NMR 電子顕微鏡小角散乱中性子線回折線維回折粉末回折赤外分光 EPR FRET 理論モデルハイブリッド
著者・登録者
ジャーナル
IF	>30 >20 >10 >5 all

タイトル	SARS-CoV-2 neutralizing antibody structures inform therapeutic strategies.
ジャーナル・号・ページ	Nature, Vol. 588, Issue 7839, Page 682-687, Year 2020
掲載日	2020年10月12日
著者	Christopher O Barnes / Claudia A Jette / Morgan E Abernathy / Kim-Marie A Dam / Shannon R Esswein / Harry B Gristick / Andrey G Malyutin / Naima G Sharaf / Kathryn E Huey-Tubman / Yu E Lee / Davide F Robbiani / Michel C Nussenzweig / Anthony P West / Pamela J Bjorkman /
PubMed 要旨	The coronavirus disease 2019 (COVID-19) pandemic presents an urgent health crisis. Human neutralizing antibodies that target the host ACE2 receptor-binding domain (RBD) of the severe acute ...The coronavirus disease 2019 (COVID-19) pandemic presents an urgent health crisis. Human neutralizing antibodies that target the host ACE2 receptor-binding domain (RBD) of the severe acute respiratory syndrome coronavirus-2 (SARS-CoV-2) spike protein show promise therapeutically and are being evaluated clinically. Here, to identify the structural correlates of SARS-CoV-2 neutralization, we solved eight new structures of distinct COVID-19 human neutralizing antibodies in complex with the SARS-CoV-2 spike trimer or RBD. Structural comparisons allowed us to classify the antibodies into categories: (1) neutralizing antibodies encoded by the VH3-53 gene segment with short CDRH3 loops that block ACE2 and bind only to 'up' RBDs; (2) ACE2-blocking neutralizing antibodies that bind both up and 'down' RBDs and can contact adjacent RBDs; (3) neutralizing antibodies that bind outside the ACE2 site and recognize both up and down RBDs; and (4) previously described antibodies that do not block ACE2 and bind only to up RBDs. Class 2 contained four neutralizing antibodies with epitopes that bridged RBDs, including a VH3-53 antibody that used a long CDRH3 with a hydrophobic tip to bridge between adjacent down RBDs, thereby locking the spike into a closed conformation. Epitope and paratope mapping revealed few interactions with host-derived N-glycans and minor contributions of antibody somatic hypermutations to epitope contacts. Affinity measurements and mapping of naturally occurring and in vitro-selected spike mutants in 3D provided insight into the potential for SARS-CoV-2 to escape from antibodies elicited during infection or delivered therapeutically. These classifications and structural analyses provide rules for assigning current and future human RBD-targeting antibodies into classes, evaluating avidity effects and suggesting combinations for clinical use, and provide insight into immune responses against SARS-CoV-2.
リンク	Nature / PubMed:33045718 / PubMed Central
手法	EM (単粒子) / X線回折
解像度	1.65 - 4.4 Å
構造データ	22729 7k8s EMDB-22729, PDB-7k8s: Structure of the SARS-CoV-2 S 2P trimer in complex with the human neutralizing antibody Fab fragment, C002 (state 1) 手法: EM (単粒子) / 解像度: 3.4 Å 22730 7k8t EMDB-22730, PDB-7k8t: Structure of the SARS-CoV-2 S 6P trimer in complex with the human neutralizing antibody Fab fragment, C002 (State 2) 手法: EM (単粒子) / 解像度: 3.4 Å 22731 7k8u EMDB-22731, PDB-7k8u: Structure of the SARS-CoV-2 S 6P trimer in complex with the human neutralizing antibody Fab fragment, C104 手法: EM (単粒子) / 解像度: 3.8 Å 22732 7k8v EMDB-22732, PDB-7k8v: Structure of the SARS-CoV-2 S 2P trimer in complex with the human neutralizing antibody Fab fragment, C110 手法: EM (単粒子) / 解像度: 3.8 Å 22733 7k8w EMDB-22733, PDB-7k8w: Structure of the SARS-CoV-2 S 2P trimer in complex with the human neutralizing antibody Fab fragment, C119 手法: EM (単粒子) / 解像度: 3.6 Å 22734 7k8x EMDB-22734, PDB-7k8x: Structure of the SARS-CoV-2 S 2P trimer in complex with the human neutralizing antibody Fab fragment, C121 (State 1) 手法: EM (単粒子) / 解像度: 3.9 Å 22735 7k8y EMDB-22735, PDB-7k8y: Structure of the SARS-CoV-2 S 2P trimer in complex with the human neutralizing antibody Fab fragment, C121 (State 2) 手法: EM (単粒子) / 解像度: 4.4 Å 22736 7k8z EMDB-22736, PDB-7k8z: Structure of the SARS-CoV-2 S 2P trimer in complex with the human neutralizing antibody Fab fragment, C135 手法: EM (単粒子) / 解像度: 3.5 Å 22737 7k90 EMDB-22737, PDB-7k90: Structure of the SARS-CoV-2 S 6P trimer in complex with the human neutralizing antibody Fab fragment, C144 手法: EM (単粒子) / 解像度: 3.24 Å PDB-7k8m: Structure of the SARS-CoV-2 receptor binding domain in complex with the human neutralizing antibody Fab fragment, C102 手法: X-RAY DIFFRACTION / 解像度: 3.2 Å PDB-7k8n: Crystal structure of an anti-SARS-CoV-2 human neutralizing antibody Fab fragment, C102 手法: X-RAY DIFFRACTION / 解像度: 1.65 Å PDB-7k8o: Crystal structure of an anti-SARS-CoV-2 human neutralizing antibody Fab fragment, C002 手法: X-RAY DIFFRACTION / 解像度: 1.95 Å PDB-7k8p: Crystal structure of an anti-SARS-CoV-2 human neutralizing antibody Fab fragment, C110 手法: X-RAY DIFFRACTION / 解像度: 1.8 Å PDB-7k8q: Crystal structure of an anti-SARS-CoV-2 human neutralizing antibody Fab fragment, C121 手法: X-RAY DIFFRACTION / 解像度: 2.0 Å PDB-7k8r: Crystal structure of an anti-SARS-CoV-2 human neutralizing antibody Fab fragment, C135 手法: X-RAY DIFFRACTION / 解像度: 2.0 Å
化合物	ChemComp-NAG: 2-acetamido-2-deoxy-beta-D-glucopyranose / N-アセチル-β-D-グルコサミン / N-アセチルグルコサミン ChemComp-SO4: SULFATE ION / 硫酸ジアニオン / 硫酸塩 ChemComp-GOL: GLYCEROL / グリセロ-ル / グリセリン ChemComp-PEG: DI(HYDROXYETHYL)ETHER / ジエチレングリコ-ル / ジエチレングリコール ChemComp-HOH: WATER / 水
由来	severe acute respiratory syndrome coronavirus 2 (SARSコロナウイルス2) homo sapiens (ヒト)
キーワード	VIRAL PROTEIN/IMMUNE SYSTEM (ウイルス性) / Human Neutralizing Antibody (中和抗体) / SARS-CoV-2 (SARSコロナウイルス2) / Receptor Binding Domain (受容体) / COVID-19 (新型コロナウイルス感染症 (2019年)) / VIRAL PROTEIN-IMMUNE SYSTEM complex (ウイルス性) / IMMUNE SYSTEM (免疫系) / spike glycoprotein (スパイクタンパク質) / monoclonal antibody (モノクローナル抗体) / neutralizing antibody (中和抗体) / PROTEIN-IMMUNE SYSTEM complex