A 193-Amino Acid Fragment of the SARS Coronavirus S Protein Efficiently Binds Angiotensin-converting Enzyme 2

By S. Wong, Wenhui Li, M. J. Moore, H. Choe, M. Farzan. Journal of Biological Chemistry, 2004

690 citations recorded by the source corpus.

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 IC50 of less than 10 nm, whereas the IC50 of the S1 domain was ∼50 nm. These data identify an independently folded receptor-binding domain of the SARS-CoV S protein.

Subfields: Animal Science and Zoology, Infectious Diseases

View Paper: https://www.semanticscholar.org/paper/7070073bf53e5ebb1b6e427e1ce70010b05edc3e

How researchers see this paper

The researchers whose trusted networks rank it highest, strongest advocate first. Every researcher gets a different order.

In Animal Science and Zoology

1. P. Masters
2. Fang Li
3. D. Veesler
4. A. Walls
5. M. A. Tortorici
6. S. Weiss
7. J. Leibowitz
8. T. S. Fung

In Infectious Diseases

1. P. Masters
2. D. Veesler
3. A. Walls
4. Fang Li
5. M. A. Tortorici
6. S. Weiss
7. Young-Jun Park
8. J. Leibowitz

Citations in the corpus

• Structure, Function, and Evolution of Coronavirus Spike Proteins (2016, background): “S1-CTDs are responsible for recognizing protein receptors ACE2, APN, and DPP4 (23, 46–51).”
• The Molecular Biology of Coronaviruses (2006, background): “The SARS-CoV RBD was more finely delimited, to amino acids 318–510, by analysis of the binding to ACE2 of a large set of S1 constructs (Wong et al., 2004).”
• Receptor and viral determinants of SARS-coronavirus adaptation to human ACE2 (2005, methodology): “Immunoprecipitations were performed as previously described Wong et al, 2004) .”