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Science 16 September 2005:
Vol. 309. no. 5742, pp. 1864 - 1868
DOI: 10.1126/science.1116480
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Reports

Structure of SARS Coronavirus Spike Receptor-Binding Domain Complexed with Receptor

Fang Li,1 Wenhui Li,3 Michael Farzan,3 Stephen C. Harrison1,2*

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.

1 Department of Biological Chemistry and Molecular Pharmacology, Harvard Medical School and Laboratory of Molecular Medicine, 320 Longwood Avenue, Boston, MA 02115, USA.
2 Howard Hughes Medical Institute, Children's Hospital, 320 Longwood Avenue, Boston, MA 02115, USA.
3 Department of Microbiology and Molecular Genetics, Harvard Medical School, New England Primate Research Center, Southborough, MA 01772, USA.

* To whom correspondence should be addressed. E-mail: harrison{at}crystal.harvard.edu

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