A 193-amino acid fragment of the SARS coronavirus S protein efficiently binds angiotensin-converting enzyme 2.
The coronavirus spike (S) protein mediates infection of receptor-expressing host cells and is a critical target for antiviral neutralizing antibodies. Angiotensin-converting enzyme 2 (ACE2) is a functional receptor for the coronavirus (severe acute respiratory syndrome (SARS)-CoV) that causes SARS. Here we demonstrate that a 193-amino acid fragment of the S protein (residues 318-510) bound ACE2 more efficiently than did the full S1 domain (residues 12-672). Smaller S protein fragments, expressing residues 327-510 or 318-490, did not detectably bind ACE2. A point mutation at aspartic acid 454 abolished association of the full S1 domain and of the 193-residue fragment with ACE2. The 193-residue fragment blocked S protein-mediated infection with an IC(50) of less than 10 nm, whereas the IC(50) of the S1 domain was approximately 50 nm. These data identify an independently folded receptor-binding domain of the SARS-CoV S protein.
Wong
Swee Kee
SK
Partners AIDS Research Center, Brigham and Women's Hospital, Department of Medicine (Microbiology and Molecular Genetics), Harvard Medical School, Boston, Massachusetts 02115, USA.
Li
Wenhui
W
Moore
Michael J
MJ
Choe
Hyeryun
H
Farzan
Michael
M
D000409:Alanine / Q000737:chemistry; D000085962:Angiotensin-Converting Enzyme 2; D002268:Carboxypeptidases / Q000737:chemistry* / Q000378:metabolism; D002460:Cell Line; D003545:Cysteine / Q000737:chemistry; D004305:Dose-Response Relationship, Drug; D004591:Electrophoresis, Polyacrylamide Gel; D005434:Flow Cytometry; D018698:Glutamic Acid / Q000737:chemistry; D006801:Humans; D020128:Inhibitory Concentration 50; D008562:Membrane Glycoproteins / Q000737:chemistry*; D009154:Mutation; D007703:Peptidyl-Dipeptidase A; D017354:Point Mutation; D011485:Protein Binding; D017434:Protein Structure, Tertiary; D045473:Severe acute respiratory syndrome-related coronavirus / Q000378:metabolism*; D064370:Spike Glycoprotein, Coronavirus; D014162:Transfection; D014759:Viral Envelope Proteins / Q000737:chemistry*
D008562:Membrane Glycoproteins; D064370:Spike Glycoprotein, Coronavirus; D014759:Viral Envelope Proteins; C578557:spike glycoprotein, SARS-CoV; C578553:spike protein, mouse hepatitis virus; D018698:Glutamic Acid; D002268:Carboxypeptidases; D007703:Peptidyl-Dipeptidase A; C000705307:ACE2 protein, human; D000085962:Angiotensin-Converting Enzyme 2; D003545:Cysteine; D000409:Alanine