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Journal of Virology, January 2003, p. 1281-1291, Vol. 77, No. 2
0022-538X/03/$08.00+0     DOI: 10.1128/JVI.77.2.1281-1291.2003
Copyright © 2003, American Society for Microbiology. All Rights Reserved.

Cytoplasmic Tail of Moloney Murine Leukemia Virus Envelope Protein Influences the Conformation of the Extracellular Domain: Implications for Mechanism of Action of the R Peptide

Hector C. Aguilar, W. French Anderson, and Paula M. Cannon*

Gene Therapy Laboratories, Keck School of Medicine, University of Southern California, Los Angeles, California 90033

Received 14 June 2002/ Accepted 22 October 2002

The envelope (Env) protein of Moloney murine leukemia virus (MoMuLV) is a homotrimeric complex whose monomers consist of linked surface (SU) and transmembrane (TM) proteins cleaved from a precursor protein by a cellular protease. In addition, a significant fraction of virion-associated TM is further processed by the viral protease to remove the C-terminal 16 amino acids of the cytoplasmic domain, the R peptide. This cleavage greatly enhances the fusogenicity of the protein and is necessary for the formation of a fully functional Env protein complex. We have previously proposed that R peptide cleavage enhances fusogenicity by altering the conformation of the ectodomain of the protein (Y. Zhao et al., J. Virol. 72:5392-5398, 1998). Using a series of truncation and point mutants of MoMuLV Env, we now provide direct biochemical and immunological evidence that the cytoplasmic tail and the membrane-spanning region of Env can influence the overall structure of the ectodomain of the protein and alter the strength of the SU-TM interaction. The R-peptide-truncated form of the protein, in particular, exhibits a markedly different conformation than the full-length protein.


* Corresponding author. Present address: Department of Microbiology and Immunology, Uniformed Services University, 4301 Jones Bridge Rd., Bethesda, MD 20814-4799. Phone: (301) 295-3402. Fax: (301) 295-1545. E-mail: pcannon{at}usuhs.mil.


Journal of Virology, January 2003, p. 1281-1291, Vol. 77, No. 2
0022-538X/03/$08.00+0     DOI: 10.1128/JVI.77.2.1281-1291.2003
Copyright © 2003, American Society for Microbiology. All Rights Reserved.