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Journal of Virology, February 2003, p. 2717-2729, Vol. 77, No. 4
0022-538X/03/$08.00+0     DOI: 10.1128/JVI.77.4.2717-2729.2003
Copyright © 2003, American Society for Microbiology. All Rights Reserved.

Structure and Mechanism of a Coreceptor for Infection by a Pathogenic Feline Retrovirus

Anna L. Barnett,1 David L. Wensel,1 Weihua Li,1 Deborah Fass,2* and James M. Cunningham1*

Department of Medicine and Howard Hughes Medical Institute, Brigham and Women's Hospital and Harvard Medical School, Boston, Massachusetts 02115,1 Department of Structural Biology, Weizmann Institute of Science, Rehovot 76100, Israel2

Received 17 June 2002/ Accepted 2 November 2002

Infection of T lymphocytes by the cytopathic retrovirus feline leukemia virus subgroup T (FeLV-T) requires FeLIX, a cellular coreceptor that is encoded by an endogenous provirus and closely resembles the receptor-binding domain (RBD) of feline leukemia virus subgroup B (FeLV-B). We determined the structure of FeLV-B RBD, which has FeLIX activity, to a 2.5-Å resolution by X-ray crystallography. The structure of the receptor-specific subdomain of this glycoprotein differs dramatically from that of Friend murine leukemia virus (Fr-MLV), which binds a different cell surface receptor. Remarkably, we find that Fr-MLV RBD also activates FeLV-T infection of cells expressing the Fr-MLV receptor and that FeLV-B RBD is a competitive inhibitor of infection under these conditions. These studies suggest that FeLV-T infection relies on the following property of mammalian leukemia virus RBDs: the ability to couple interaction with one of a variety of receptors to the activation of a conserved membrane fusion mechanism. A comparison of the FeLV-B and Fr-MLV RBD structures illustrates how receptor-specific regions are linked to conserved elements critical for postbinding events in virus entry.


* Corresponding author. Mailing address for James M. Cunningham: Rm. 1030, Thorn Building, Brigham and Women's Hospital, 75 Francis St., Boston, MA 02115. Phone: (617) 732-5852. Fax: (617) 738-5575. E-mail: cunningham{at}rascal.med.harvard.edu. Mailing address for Deborah Fass: Department of Structural Biology, Weizmann Institute of Science, Rehovot 76100, Israel. Phone: 011-8-9343214. Fax: 011-8-9344136. E-mail: deborah.fass@weizmann.ac.il.


Journal of Virology, February 2003, p. 2717-2729, Vol. 77, No. 4
0022-538X/03/$08.00+0     DOI: 10.1128/JVI.77.4.2717-2729.2003
Copyright © 2003, American Society for Microbiology. All Rights Reserved.




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