Database of articles cited by EMDB/PDB/SASBDB data

Keywords
Structure methods	All X-ray diffraction NMR electron microscopy small angle scattering neutron diffraction fiber diffraction powder diffraction infrared spectroscopy EPR fluorescence transfer theoretical model Hybrid
Author
Journal
IF	>30 >20 >10 >5 all

Title	SARS-CoV-2 neutralizing antibody structures inform therapeutic strategies.
Journal, issue, pages	Nature, Vol. 588, Issue 7839, Page 682-687, Year 2020
Publish date	Oct 12, 2020
Authors	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 Abstract	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.
External links	Nature / PubMed:33045718 / PubMed Central
Methods	EM (single particle) / X-ray diffraction
Resolution	1.65 - 4.4 Å
Structure data	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) Method: EM (single particle) / Resolution: 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) Method: EM (single particle) / Resolution: 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 Method: EM (single particle) / Resolution: 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 Method: EM (single particle) / Resolution: 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 Method: EM (single particle) / Resolution: 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) Method: EM (single particle) / Resolution: 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) Method: EM (single particle) / Resolution: 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 Method: EM (single particle) / Resolution: 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 Method: EM (single particle) / Resolution: 3.24 Å PDB-7k8m: Structure of the SARS-CoV-2 receptor binding domain in complex with the human neutralizing antibody Fab fragment, C102 Method: X-RAY DIFFRACTION / Resolution: 3.2 Å PDB-7k8n: Crystal structure of an anti-SARS-CoV-2 human neutralizing antibody Fab fragment, C102 Method: X-RAY DIFFRACTION / Resolution: 1.65 Å PDB-7k8o: Crystal structure of an anti-SARS-CoV-2 human neutralizing antibody Fab fragment, C002 Method: X-RAY DIFFRACTION / Resolution: 1.95 Å PDB-7k8p: Crystal structure of an anti-SARS-CoV-2 human neutralizing antibody Fab fragment, C110 Method: X-RAY DIFFRACTION / Resolution: 1.8 Å PDB-7k8q: Crystal structure of an anti-SARS-CoV-2 human neutralizing antibody Fab fragment, C121 Method: X-RAY DIFFRACTION / Resolution: 2.0 Å PDB-7k8r: Crystal structure of an anti-SARS-CoV-2 human neutralizing antibody Fab fragment, C135 Method: X-RAY DIFFRACTION / Resolution: 2.0 Å
Chemicals	ChemComp-NAG: 2-acetamido-2-deoxy-beta-D-glucopyranose / N-Acetylglucosamine ChemComp-SO4: SULFATE ION / Sulfate ChemComp-GOL: GLYCEROL / Glycerol ChemComp-PEG: DI(HYDROXYETHYL)ETHER / Diethylene glycol ChemComp-HOH: WATER / Water
Source	severe acute respiratory syndrome coronavirus 2 homo sapiens (human)
Keywords	VIRAL PROTEIN/IMMUNE SYSTEM / Human Neutralizing Antibody / SARS-CoV-2 / Receptor Binding Domain / COVID-19 / VIRAL PROTEIN-IMMUNE SYSTEM complex / IMMUNE SYSTEM / spike glycoprotein / monoclonal antibody / neutralizing antibody / PROTEIN-IMMUNE SYSTEM complex