|
Basic Characteristics of Mutations
|
|
Mutation Site
|
P384A |
|
Mutation Site Sentence
|
CR3022 does not neutralize SARS-CoV-2,but the increased affinity to SARS-CoV-2 P384A mutant now enables neutralization with a similar potency to SARS-CoV. |
|
Mutation Level
|
Amino acid level |
|
Mutation Type
|
Nonsynonymous substitution |
|
Gene/Protein/Region
|
RBD |
|
Standardized Encoding Gene
|
S
|
|
Genotype/Subtype
|
- |
|
Viral Reference
|
-
|
|
Functional Impact and Mechanisms
|
|
Disease
|
COVID-19
|
|
Immune
|
Y |
|
Target Gene
|
-
|
|
Clinical and Epidemiological Correlations
|
|
Clinical Information
|
- |
|
Treatment
|
- |
|
Location
|
- |
|
Literature Information
|
|
PMID
|
33275640
|
|
Title
|
A natural mutation between SARS-CoV-2 and SARS-CoV determines neutralization by a cross-reactive antibody
|
|
Author
|
Wu NC,Yuan M,Bangaru S,Huang D,Zhu X,Lee CD,Turner HL,Peng L,Yang L,Burton DR,Nemazee D,Ward AB,Wilson IA
|
|
Journal
|
PLoS pathogens
|
|
Journal Info
|
2020 Dec 4;16(12):e1009089
|
|
Abstract
|
Epitopes that are conserved among SARS-like coronaviruses are attractive targets for design of cross-reactive vaccines and therapeutics. CR3022 is a SARS-CoV neutralizing antibody to a highly conserved epitope on the receptor binding domain (RBD) on the spike protein that is able to cross-react with SARS-CoV-2, but with lower affinity. Using x-ray crystallography, mutagenesis, and binding experiments, we illustrate that of four amino acid differences in the CR3022 epitope between SARS-CoV-2 and SARS-CoV, a single mutation P384A fully determines the affinity difference. CR3022 does not neutralize SARS-CoV-2, but the increased affinity to SARS-CoV-2 P384A mutant now enables neutralization with a similar potency to SARS-CoV. We further investigated CR3022 interaction with the SARS-CoV spike protein by negative-stain EM and cryo-EM. Three CR3022 Fabs bind per trimer with the RBD observed in different up-conformations due to considerable flexibility of the RBD. In one of these conformations, quaternary interactions are made by CR3022 to the N-terminal domain (NTD) of an adjacent subunit. Overall, this study provides insights into antigenic variation and potential cross-neutralizing epitopes on SARS-like viruses.
|
|
Sequence Data
|
-
|
|
|