Abstract
The spike protein (S) of SARS coronavirus (SARS-CoV) attaches the virus to its cellular receptor, angiotensin-converting enzyme 2 (ACE2). A defined receptor-binding domain (RBD) on S mediates this interaction. The crystal structure at 2.9 angstrom resolution of the RBD bound with the peptidase domain of human ACE2 shows that the RBD presents a gently concave surface, which cradles the N-terminal lobe of the peptidase. The atomic details at the interface between the two proteins clarify the importance of residue changes that facilitate efficient cross-species infection and human-to-human transmission. The structure of the RBD suggests ways to make truncated disulfide-stabilized RBD variants for use in the design of coronavirus vaccines.
Publication types
- Research Support, N.I.H., Extramural
- Research Support, Non-U.S. Gov't
- Research Support, U.S. Gov't, P.H.S.
MeSH terms
- Amino Acid Sequence
- Amino Acid Substitution
- Angiotensin-Converting Enzyme 2
- Animals
- Antibodies, Viral / immunology
- Binding Sites
- Carboxypeptidases / chemistry*
- Carboxypeptidases / metabolism
- Cell Line
- Crystallography, X-Ray
- Disease Outbreaks
- Epitopes
- Glycosylation
- Humans
- Hydrophobic and Hydrophilic Interactions
- Membrane Glycoproteins / chemistry*
- Membrane Glycoproteins / genetics
- Membrane Glycoproteins / immunology
- Membrane Glycoproteins / metabolism*
- Models, Molecular
- Molecular Sequence Data
- Mutation
- Peptidyl-Dipeptidase A
- Protein Conformation
- Protein Structure, Tertiary
- Receptors, Virus / chemistry*
- Receptors, Virus / metabolism
- Severe Acute Respiratory Syndrome / transmission
- Severe Acute Respiratory Syndrome / virology*
- Severe acute respiratory syndrome-related coronavirus / chemistry*
- Severe acute respiratory syndrome-related coronavirus / genetics
- Severe acute respiratory syndrome-related coronavirus / physiology
- Species Specificity
- Spike Glycoprotein, Coronavirus
- Viral Envelope Proteins / chemistry*
- Viral Envelope Proteins / genetics
- Viral Envelope Proteins / immunology
- Viral Envelope Proteins / metabolism*
- Viral Vaccines
- Viverridae / virology
Substances
- Antibodies, Viral
- Epitopes
- Membrane Glycoproteins
- Receptors, Virus
- Spike Glycoprotein, Coronavirus
- Viral Envelope Proteins
- Viral Vaccines
- spike glycoprotein, SARS-CoV
- Carboxypeptidases
- Peptidyl-Dipeptidase A
- ACE2 protein, human
- Angiotensin-Converting Enzyme 2