Structure of SARS coronavirus spike receptor-binding domain complexed with receptor.
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.
Li
Fang
F
Department of Biological Chemistry and Molecular Pharmacology, Harvard Medical School and Laboratory of Molecular Medicine, 320 Longwood Avenue, Boston, MA 02115, USA.
Li
Wenhui
W
Farzan
Michael
M
Harrison
Stephen C
SC
D000595:Amino Acid Sequence; D019943:Amino Acid Substitution; D000085962:Angiotensin-Converting Enzyme 2; D000818:Animals; D000914:Antibodies, Viral / Q000276:immunology; D001665:Binding Sites; D002268:Carboxypeptidases / Q000737:chemistry* / Q000378:metabolism; D002460:Cell Line; D018360:Crystallography, X-Ray; D004196:Disease Outbreaks; D000939:Epitopes; D006031:Glycosylation; D006801:Humans; D057927:Hydrophobic and Hydrophilic Interactions; D008562:Membrane Glycoproteins / Q000737:chemistry* / Q000235:genetics / Q000276:immunology / Q000378:metabolism*; D008958:Models, Molecular; D008969:Molecular Sequence Data; D009154:Mutation; D007703:Peptidyl-Dipeptidase A; D011487:Protein Conformation; D017434:Protein Structure, Tertiary; D011991:Receptors, Virus / Q000737:chemistry* / Q000378:metabolism; D045473:Severe acute respiratory syndrome-related coronavirus / Q000737:chemistry* / Q000235:genetics / Q000502:physiology; D045169:Severe Acute Respiratory Syndrome / Q000635:transmission / Q000821:virology*; D013045:Species Specificity; D064370:Spike Glycoprotein, Coronavirus; D014759:Viral Envelope Proteins / Q000737:chemistry* / Q000235:genetics / Q000276:immunology / Q000378:metabolism*; D014765:Viral Vaccines; D045949:Viverridae / Q000821:virology
D000914:Antibodies, Viral; D000939:Epitopes; D008562:Membrane Glycoproteins; D011991:Receptors, Virus; D064370:Spike Glycoprotein, Coronavirus; D014759:Viral Envelope Proteins; D014765:Viral Vaccines; C578557:spike glycoprotein, SARS-CoV; D002268:Carboxypeptidases; D007703:Peptidyl-Dipeptidase A; C000705307:ACE2 protein, human; D000085962:Angiotensin-Converting Enzyme 2