Modular basis for potent SARS-CoV-2 neutralization by a prevalent VH1-2-derived antibody class.
Cell Rep
; 35(1): 108950, 2021 04 06.
Article
en En
| MEDLINE
| ID: mdl-33794145
ABSTRACT
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 F486RBD. 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.
Palabras clave
Texto completo:
1
Banco de datos:
MEDLINE
Asunto principal:
Región Variable de Inmunoglobulina
/
Anticuerpos Neutralizantes
/
SARS-CoV-2
/
COVID-19
/
Anticuerpos Antivirales
Tipo de estudio:
Prognostic_studies
Límite:
Humans
Idioma:
En
Año:
2021
Tipo del documento:
Article