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Journal of Virology, July 2006, p. 6794-6800, Vol. 80, No. 14
0022-538X/06/$08.00+0     doi:10.1128/JVI.02744-05
Copyright © 2006, American Society for Microbiology. All Rights Reserved.

Conformational States of the Severe Acute Respiratory Syndrome Coronavirus Spike Protein Ectodomain

Fang Li,1 Marcelo Berardi,2 Wenhui Li,3 Michael Farzan,3 Philip R. Dormitzer,1 and Stephen C. Harrison1,2,4*

Laboratory of Molecular Medicine, Children's Hospital,1 Department of Biological Chemistry and Molecular Pharmacology, Harvard Medical School, Boston, Massachusetts 02115,2 Department of Microbiology and Molecular Genetics, Harvard Medical School, and New England Primate Center, Southborough, Massachusetts 01772,3 Howard Hughes Medical Institute, Boston, Massachusetts 021154

Received 30 December 2005/ Accepted 3 May 2006

The severe acute respiratory syndrome coronavirus enters cells through the activities of a spike protein (S) which has receptor-binding (S1) and membrane fusion (S2) regions. We have characterized four sequential states of a purified recombinant S ectodomain (S-e) comprising S1 and the ectodomain of S2. They are S-e monomers, uncleaved S-e trimers, cleaved S-e trimers, and dissociated S1 monomers and S2 trimer rosettes. Lowered pH induces an irreversible transition from flexible, L-shaped S-e monomers to clove-shaped trimers. Protease cleavage of the trimer occurs at the S1-S2 boundary; an ensuing S1 dissociation leads to a major rearrangement of the trimeric S2 and to formation of rosettes likely to represent clusters of elongated, postfusion trimers of S2 associated through their fusion peptides. The states and transitions of S suggest conformational changes that mediate viral entry into cells.

* Corresponding author. Mailing address: HHMI/Children's Hospital, Laboratory of Molecular Medicine, 320 Longwood Ave., Boston, MA 02115. Phone: (617) 355-7372. Fax: (617) 730-1967. E-mail: harrison{at}crystal.harvard.edu.

Journal of Virology, July 2006, p. 6794-6800, Vol. 80, No. 14
0022-538X/06/$08.00+0     doi:10.1128/JVI.02744-05
Copyright © 2006, American Society for Microbiology. All Rights Reserved.



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