EMD-32736

Single-particle
2.47 Å
EMD-32736 Deposition: 27/01/2022
Map released: 23/03/2022
Last modified: 30/10/2024
Overview 3D View Sample Experiment Validation Volume Browser Additional data Links
Overview 3D View Sample Experiment Validation Volume Browser Additional data Links

EMD-32736

The interface of JMB2002 Fab binds to SARS-CoV-2 Omicron Variant S

EMD-32736

Single-particle
2.47 Å
EMD-32736 Deposition: 27/01/2022
Map released: 23/03/2022
Last modified: 30/10/2024
Overview 3D View Sample Experiment Validation Volume Browser Additional data Links
Sample Organism: Mus musculus, Severe acute respiratory syndrome coronavirus 2
Sample: SARS-CoV-2 Omicron Variant S Trimer complexed with JMB2002 Fab
Fitted models: 7wrv (Avg. Q-score: 0.507)

Deposition Authors: Yin W , Xu Y , Xu P , Cao X , Wu C , Gu C , He X , Wang X , Huang S , Yuan Q, Wu K, Hu W, Huang Z , Liu J, Wang Z , Jia F, Xia K , Liu P, Wang X , Song B , Zheng J , Jiang H , Cheng X , Jiang Y , Deng SJ , Xu HE
Structures of the Omicron spike trimer with ACE2 and an anti-Omicron antibody.
Yin W , Xu Y , Xu P , Cao X , Wu C , Gu C , He X , Wang X , Huang S , Yuan Q, Wu K, Hu W, Huang Z , Liu J, Wang Z , Jia F, Xia K , Liu P, Wang X , Song B , Zheng J , Jiang H , Cheng X , Jiang Y , Deng SJ , Xu HE
(2022) Science , 375 , 1048 - 1053
PUBMED: 35133176
DOI: doi:10.1126/science.abn8863
ISSN: 1095-9203
ASTM: SCIEAS
Abstract:
The severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) Omicron variant has become the dominant infective strain. We report the structures of the Omicron spike trimer on its own and in complex with angiotensin-converting enzyme 2 (ACE2) or an anti-Omicron antibody. Most Omicron mutations are located on the surface of the spike protein and change binding epitopes to many current antibodies. In the ACE2-binding site, compensating mutations strengthen receptor binding domain (RBD) binding to ACE2. Both the RBD and the apo form of the Omicron spike trimer are thermodynamically unstable. An unusual RBD-RBD interaction in the ACE2-spike complex supports the open conformation and further reinforces ACE2 binding to the spike trimer. A broad-spectrum therapeutic antibody, JMB2002, which has completed a phase 1 clinical trial, maintains neutralizing activity against Omicron. JMB2002 binds to RBD differently from other characterized antibodies and inhibits ACE2 binding.