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

Science
16 Sep 2005
Vol 309, Issue 5742
pp. 1864-1868

Abstract

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.

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Single-letter abbreviations for the amino acid residues are as follows: A, Ala; C, Cys; D, Asp; E, Glu; F, Phe; G, Gly; H, His; I, Ile; K, Lys; L, Leu; M, Met; N, Asn; P, Pro; Q, Gln; R, Arg; S, Ser; T, Thr; V, Val; W, Trp; and Y, Tyr.
37
We thank staff at the Advanced Light Source beam-lines 8.2.1 and 8.2.2 for assistance and M. Berardi and E. Settembre for discussions. This work was supported by NIH grants CA13202 (to S.C.H.) and AI061601 (to M.R.F.). S.C.H. is an Investigator in the Howard Hughes Medical Institute. Coordinates and structure factors have been submitted to the Protein Data Bank with accession number 2AJF.

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Published In

Science
Volume 309 | Issue 5742
16 September 2005

Submission history

Received: 22 June 2005
Accepted: 11 August 2005
Published in print: 16 September 2005

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Notes

Supporting Online Material
www.sciencemag.org/cgi/content/full/309/5742/1864/DC1
Materials and Methods
Figs. S1 to S4
Table S1
References

Authors

Affiliations

Fang Li
Department of Biological Chemistry and Molecular Pharmacology, Harvard Medical School and Laboratory of Molecular Medicine, 320 Longwood Avenue, Boston, MA 02115, USA.
Wenhui Li
Department of Microbiology and Molecular Genetics, Harvard Medical School, New England Primate Research Center, Southborough, MA 01772, USA.
Michael Farzan
Department of Microbiology and Molecular Genetics, Harvard Medical School, New England Primate Research Center, Southborough, MA 01772, USA.
Stephen C. Harrison* [email protected]
Department of Biological Chemistry and Molecular Pharmacology, Harvard Medical School and Laboratory of Molecular Medicine, 320 Longwood Avenue, Boston, MA 02115, USA.
Howard Hughes Medical Institute, Children's Hospital, 320 Longwood Avenue, Boston, MA 02115, USA.

Notes

*
To whom correspondence should be addressed. E-mail: [email protected]

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