Structural insights into immune recognition of the severe acute respiratory syndrome coronavirus S protein receptor binding domain

John E Pak; Chetna Sharon; Malathy Satkunarajah; Thierry C Auperin; Cheryl M Cameron; David J Kelvin; Jayaraman Seetharaman; Alan Cochrane; Francis A Plummer; Jody D Berry; James M Rini

doi:10.1016/j.jmb.2009.03.042

Structural insights into immune recognition of the severe acute respiratory syndrome coronavirus S protein receptor binding domain

J Mol Biol. 2009 May 15;388(4):815-23. doi: 10.1016/j.jmb.2009.03.042. Epub 2009 Mar 24.

Authors

John E Pak¹, Chetna Sharon, Malathy Satkunarajah, Thierry C Auperin, Cheryl M Cameron, David J Kelvin, Jayaraman Seetharaman, Alan Cochrane, Francis A Plummer, Jody D Berry, James M Rini

Affiliation

¹ Department of Molecular Genetics, University of Toronto, Toronto, Ontario, Canada.

Abstract

The spike (S) protein of the severe acute respiratory syndrome coronavirus (SARS-CoV) is responsible for host cell attachment and fusion of the viral and host cell membranes. Within S the receptor binding domain (RBD) mediates the interaction with angiotensin-converting enzyme 2 (ACE2), the SARS-CoV host cell receptor. Both S and the RBD are highly immunogenic and both have been found to elicit neutralizing antibodies. Reported here is the X-ray crystal structure of the RBD in complex with the Fab of a neutralizing mouse monoclonal antibody, F26G19, elicited by immunization with chemically inactivated SARS-CoV. The RBD-F26G19 Fab complex represents the first example of the structural characterization of an antibody elicited by an immune response to SARS-CoV or any fragment of it. The structure reveals that the RBD surface recognized by F26G19 overlaps significantly with the surface recognized by ACE2 and, as such, suggests that F26G19 likely neutralizes SARS-CoV by blocking the virus-host cell interaction.

Publication types

Research Support, Non-U.S. Gov't

MeSH terms

Angiotensin-Converting Enzyme 2
Animals
Antibodies, Monoclonal / chemistry
Antibodies, Monoclonal / immunology
Antibody Formation / immunology
Binding Sites
Cell Line
Crystallography, X-Ray
Humans
Immunoglobulin Fab Fragments / chemistry
Immunoglobulin Fab Fragments / immunology
Membrane Glycoproteins / chemistry*
Membrane Glycoproteins / genetics
Membrane Glycoproteins / immunology*
Mice
Models, Molecular
Molecular Sequence Data
Peptidyl-Dipeptidase A* / chemistry
Peptidyl-Dipeptidase A* / immunology
Protein Structure, Tertiary*
Recombinant Fusion Proteins / genetics
Recombinant Fusion Proteins / metabolism
Severe acute respiratory syndrome-related coronavirus / immunology*
Spike Glycoprotein, Coronavirus
Viral Envelope Proteins / chemistry*
Viral Envelope Proteins / genetics
Viral Envelope Proteins / immunology*

Substances

Antibodies, Monoclonal
Immunoglobulin Fab Fragments
Membrane Glycoproteins
Recombinant Fusion Proteins
Spike Glycoprotein, Coronavirus
Viral Envelope Proteins
spike glycoprotein, SARS-CoV
spike protein, mouse hepatitis virus
Peptidyl-Dipeptidase A
ACE2 protein, human
Ace2 protein, mouse
Angiotensin-Converting Enzyme 2

Associated data

PDB/3BGF