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Journal of Virology, May 1999, p. 3758-3763, Vol. 73, No. 5
0022-538X/99/$04.00+0
Copyright © 1999, American Society for Microbiology. All rights reserved.

Identification of a Receptor-Binding Pocket on the Envelope Protein of Friend Murine Leukemia Virus

Robert A. Davey, Yi Zuo, and James M. Cunningham*

Howard Hughes Medical Institute and Division of Hematology/Oncology, Department of Medicine, Brigham and Women's Hospital and Harvard Medical School, Boston, Massachusetts 02115

Received 16 November 1998/Accepted 27 January 1999

Based on previous structural and functional studies, a potential receptor-binding site composed of residues that form a pocket at one end of the two long antiparallel helices in the receptor-binding domain of Friend 57 murine leukemia virus envelope protein (RBD) has been proposed. To test this hypothesis, directed substitutions for residues in the pocket were introduced and consequences for infection and for receptor binding were measured. Receptor binding was measured initially by a sensitive assay based on coexpression of receptor and RBD in Xenopus oocytes, and the findings were confirmed by using purified proteins. Three residues that are critical for both binding and infection (S84, D86, and W102), with side chains that extend into the pocket, were identified. Moreover, when mCAT-1 was overexpressed, the infectivity of Fr57-MLV carrying pocket substitutions was partially restored. Substitutions for 18 adjacent residues and 11 other previously unexamined surface-exposed residues outside of the RBD pocket had no detectable effect on function. Taken together, these findings support a model in which the RBD pocket interacts directly with mCAT-1 (likely residues, Y235 and E237) and multiple receptor-envelope complexes are required to form the fusion pore.

* Corresponding author. Mailing address: Room 1030 Thorn Bldg., Brigham and Women's Hospital, 20 Shattuck St., Boston, MA 02115. Phone: (617) 732-5852. Fax: (617) 730-2834. E-mail: cunningham{at}rascal.med.harvard.edu.

Journal of Virology, May 1999, p. 3758-3763, Vol. 73, No. 5
0022-538X/99/$04.00+0
Copyright © 1999, American Society for Microbiology. All rights reserved.


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