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TitleModular basis for potent SARS-CoV-2 neutralization by a prevalent VH1-2-derived antibody class.
Journal, issue, pagesCell Rep, Vol. 35, Issue 1, Page 108950, Year 2021
Publish dateApr 6, 2021
AuthorsMicah Rapp / Yicheng Guo / Eswar R Reddem / Jian Yu / Lihong Liu / Pengfei Wang / Gabriele Cerutti / Phinikoula Katsamba / Jude S Bimela / Fabiana A Bahna / Seetha M Mannepalli / Baoshan Zhang / Peter D Kwong / Yaoxing Huang / David D Ho / Lawrence Shapiro / Zizhang Sheng /
PubMed AbstractAntibodies with heavy chains that derive from the VH1-2 gene constitute some of the most potent severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2)-neutralizing antibodies yet identified. To ...Antibodies with heavy chains that derive from the VH1-2 gene constitute some of the most potent severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2)-neutralizing antibodies yet identified. To provide insight into whether these genetic similarities inform common modes of recognition, we determine the structures of the SARS-CoV-2 spike in complex with three VH1-2-derived antibodies: 2-15, 2-43, and H4. All three use VH1-2-encoded motifs to recognize the receptor-binding domain (RBD), with heavy-chain N53I-enhancing binding and light-chain tyrosines recognizing F486. Despite these similarities, class members bind both RBD-up and -down conformations of the spike, with a subset of antibodies using elongated CDRH3s to recognize glycan N343 on a neighboring RBD-a quaternary interaction accommodated by an increase in RBD separation of up to 12 Å. The VH1-2 antibody class, thus, uses modular recognition encoded by modular genetic elements to effect potent neutralization, with the VH-gene component specifying recognition of RBD and the CDRH3 component specifying quaternary interactions.
External linksCell Rep / PubMed:33794145 / PubMed Central
MethodsEM (single particle) / X-ray diffraction
Resolution3.18 - 5.87 Å
Structure data

EMDB-23165, PDB-7l56:
Cryo-EM structure of the SARS-CoV-2 spike glycoprotein bound to Fab 2-43
Method: EM (single particle) / Resolution: 3.6 Å

EMDB-23166, PDB-7l57:
Cryo-EM structure of the SARS-CoV-2 spike glycoprotein bound to Fab 2-15
Method: EM (single particle) / Resolution: 5.87 Å

EMDB-23167, PDB-7l58:
Cryo-EM structure of the SARS-CoV-2 spike glycoprotein bound to Fab H4
Method: EM (single particle) / Resolution: 5.07 Å

PDB-7l5b:
Crystallographic structure of neutralizing antibody 2-15 in complex with SARS-CoV-2 spike receptor-binding Domain (RBD).
Method: X-RAY DIFFRACTION / Resolution: 3.18 Å

Chemicals

ChemComp-NAG:
2-acetamido-2-deoxy-beta-D-glucopyranose / N-Acetylglucosamine

Source
  • homo sapiens (human)
  • severe acute respiratory syndrome coronavirus 2
KeywordsVIRAL PROTEIN/Immune System / SARS-CoV-2 / spike / glycoprotein / antibody / VIRAL PROTEIN / VIRAL PROTEIN-Immune System complex / Spike protein S1 / receptor binding protein SARS COV-2

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