Journal article
Membrane-proximal cytoplasmic domain of Moloney murine leukemia virus envelope tail facilitates fusion
Experimental and molecular pathology, Vol.84(1), pp.18-30
2008
Handle:
https://hdl.handle.net/2376/118014
PMID: 18222422
Abstract
Removal of the R peptide (residues 617–632) from the Moloney murine leukemia virus (MoMuLV) envelope protein (Env) cytoplasmic tail potentiates fusion. We examined the role of the membrane-proximal cytoplasmic domain (598–616) of the MoMuLV Env in the Env-mediated membrane fusion and incorporation. The Env truncated at 616 exhibits maximum fusogenicity in cell-to-cell fusion assay. By comparison, full tail Env (632) and the Env truncated to residue 601 mediated fusion at 40%. The Envs truncated to residues 598 or 595 are not fusogenic. Progressive cytoplasmic tail truncation correlated with decreased Env incorporation into virions. Substitution of the domain 598–616 with an amphiphilic α-helix from melittin results in maximally fusogenic Envs that efficiently incorporated into transduction competent virions. However, substitution of the domain 598–616 with random or hydrophilic sequences caused loss of the Env fusogenicity and titer while retaining incorporation. Further, a secondary structure prediction analysis of 27 unrelated Env cytoplasmic tails indicates a common (23/27) propensity for an amphiphilic α-helical domain at immediate proximity to the viral membrane. These results support the suggestion that viral fusion is enhanced by a membrane-proximal cytoplasmic amphiphilic α-helix in Env tail. The model of its action is proposed.
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Details
- Title
- Membrane-proximal cytoplasmic domain of Moloney murine leukemia virus envelope tail facilitates fusion
- Creators
- Yanina Rozenberg-Adler - San Diego Cancer Research Institute, 1200 Garden View, Suite 200, Encinitas, CA 92024, USAJohn Conner - Formerly: Gene Therapy Laboratories, Norris Cancer Center, University of Southern California School of Medicine, Los Angeles, CA 90033, USAHector Aguilar-Carreno - Department of Microbiology, Immunology and Molecular Genetics, UCLA, Los Angeles, CA 90095, USASamitabh Chakraborti - Protein Interactions Group, CCRNP, NCI-Frederick, NIH, Frederick, MD 21702, USADimiter S Dimitrov - Protein Interactions Group, CCRNP, NCI-Frederick, NIH, Frederick, MD 21702, USAW. French Anderson - Formerly: Gene Therapy Laboratories, Norris Cancer Center, University of Southern California School of Medicine, Los Angeles, CA 90033, USA
- Publication Details
- Experimental and molecular pathology, Vol.84(1), pp.18-30
- Academic Unit
- Paul G. Allen School for Global Animal Health
- Publisher
- Elsevier Inc
- Identifiers
- 99900547854501842
- Language
- English
- Resource Type
- Journal article