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Papers In Press, published online ahead of print December 11, 2003
Department of Medicine, Harvard Medical School, Cambridge, MA 02139
Corresponding Author: farzan{at}mbcrr.harvard.edu
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 (SARS-CoV) that causes severe acute respiratory syndrome (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 IC50 of less than 10 nM, whereas the IC50 of the S1 domain was approximately 50 nM. These data identify an independently folded receptor-binding domain of the SARS-CoV S protein.
J. Biol. Chem, 10.1074/jbc.C300520200
Submitted on December 2, 2003
Revised on December 11, 2003
Accepted on December 11, 2003
A 193-amino-acid fragment of the SARS coronavirus S protein efficiently binds angiotensin-converting enzyme 2
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