EMD-41382
Antibody N3-1 bound to RBD in the up conformation
EMD-41382
Single-particle3.2 Å
Deposition: 29/07/2023Map released: 17/01/2024
Last modified: 06/11/2024
Sample Organism:
Homo sapiens,
Severe acute respiratory syndrome coronavirus 2
Sample: The complex of N3-1 Fab bound to one receptor binding domain of the spike
Fitted models: 8tma (Avg. Q-score: 0.501)
Deposition Authors: Hsieh C-L, McLellan JS
Sample: The complex of N3-1 Fab bound to one receptor binding domain of the spike
Fitted models: 8tma (Avg. Q-score: 0.501)
Deposition Authors: Hsieh C-L, McLellan JS
SARS-COV-2 Omicron variants conformationally escape a rare quaternary antibody binding mode.
Goike J,
Hsieh CL ,
Horton AP ,
Gardner EC,
Zhou L,
Bartzoka F ,
Wang N,
Javanmardi K,
Herbert A,
Abbassi S,
Xie X ,
Xia H ,
Shi PY ,
Renberg R ,
Segall-Shapiro TH,
Terrace CI,
Wu W,
Shroff R,
Byrom M,
Ellington AD ,
Marcotte EM ,
Musser JM,
Kuchipudi SV ,
Kapur V,
Georgiou G ,
Weaver SC ,
Dye JM,
Boutz DR ,
McLellan JS ,
Gollihar JD
(2023) Commun Biol , 6 , 1250 - 1250
,
Horton AP ,
Gardner EC,
Zhou L,
Bartzoka F ,
Wang N,
Javanmardi K,
Herbert A,
Abbassi S,
Xie X ,
Xia H ,
Shi PY ,
Renberg R ,
Segall-Shapiro TH,
Terrace CI,
Wu W,
Shroff R,
Byrom M,
Ellington AD ,
Marcotte EM ,
Musser JM,
Kuchipudi SV ,
Kapur V,
Georgiou G ,
Weaver SC ,
Dye JM,
Boutz DR ,
McLellan JS ,
Gollihar JD
(2023) Commun Biol , 6 , 1250 - 1250
Abstract:
The ongoing evolution of SARS-CoV-2 into more easily transmissible and infectious variants has provided unprecedented insight into mutations enabling immune escape. Understanding how these mutations affect the dynamics of antibody-antigen interactions is crucial to the development of broadly protective antibodies and vaccines. Here we report the characterization of a potent neutralizing antibody (N3-1) identified from a COVID-19 patient during the first disease wave. Cryogenic electron microscopy revealed a quaternary binding mode that enables direct interactions with all three receptor-binding domains of the spike protein trimer, resulting in extraordinary avidity and potent neutralization of all major variants of concern until the emergence of Omicron. Structure-based rational design of N3-1 mutants improved binding to all Omicron variants but only partially restored neutralization of the conformationally distinct Omicron BA.1. This study provides new insights into immune evasion through changes in spike protein dynamics and highlights considerations for future conformationally biased multivalent vaccine designs.
The ongoing evolution of SARS-CoV-2 into more easily transmissible and infectious variants has provided unprecedented insight into mutations enabling immune escape. Understanding how these mutations affect the dynamics of antibody-antigen interactions is crucial to the development of broadly protective antibodies and vaccines. Here we report the characterization of a potent neutralizing antibody (N3-1) identified from a COVID-19 patient during the first disease wave. Cryogenic electron microscopy revealed a quaternary binding mode that enables direct interactions with all three receptor-binding domains of the spike protein trimer, resulting in extraordinary avidity and potent neutralization of all major variants of concern until the emergence of Omicron. Structure-based rational design of N3-1 mutants improved binding to all Omicron variants but only partially restored neutralization of the conformationally distinct Omicron BA.1. This study provides new insights into immune evasion through changes in spike protein dynamics and highlights considerations for future conformationally biased multivalent vaccine designs.