Journal article
Binding of the human immunodeficiency virus type 1 Gag polyprotein to cyclophilin A is mediated by the central region of capsid and requires Gag dimerization
Journal of virology, Vol.70(7), pp.4299-4310
07/1996
DOI: 10.1128/JVI.70.7.4299-4310.1996
PMCID: PMC190362
PMID: 8676452
Abstract
The cellular peptidyl-prolyl isomerase cyclophilin A (CyPA) is incorporated into human immunodeficiency virus type 1 (HIV-1) virions via direct contacts with the HIV-1 Gag polyprotein. Disruption of the Gag-CyPA interaction leads to the production of HIV-1 particles lacking CyPA; these virions are noninfectious, indicating that contacts between CyPA and Gag are necessary for HIV-1 replication. Here, we have used the yeast two-hybrid system in conjunction with an in vitro binding assay to identify the minimal domain of Gag required for binding to CyPA. Analysis of a panel of gag deletion mutants in the two-hybrid system indicated that a region spanning the central portion of the capsid (CA) domain was sufficient for interactions with CyPA, but discrepancies between results obtained in different fusion protein contexts suggested that multimerization of Gag might also be necessary for binding to CyPA. Consistent with a requirement for multimerization, the binding of Gag to CyPA in vitro required a region within the nucleocapsid (NC) domain shown previously to be important for Gag self-association. Substitution of a heterologous dimerization motif for the region from NC also promoted specific binding to CyPA, confirming that interactions with CyPA are dependent on Gag multimerization. Fusion of the heterologous dimerization motif to a 100-amino-acid domain from CA was sufficient for binding to CyPA in vitro. These results define the minimal CyPA-binding domain within Gag and provide insight into the mechanism by which CyPA is incorporated into HIV-1 virions.
Details
- Title: Subtitle
- Binding of the human immunodeficiency virus type 1 Gag polyprotein to cyclophilin A is mediated by the central region of capsid and requires Gag dimerization
- Creators
- J Colgan - Department of Microbiology, College of Physicians and Surgeons of Columbia University, New York, New York 10032USAHannah En Hui Yuan - Department of Microbiology, College of Physicians and Surgeons of Columbia University, New York, New York 10032USAEttaly Kara Franke - Department of Microbiology, College of Physicians and Surgeons of Columbia University, New York, New York 10032USAJeremy Luban - Department of Microbiology, College of Physicians and Surgeons of Columbia University, New York, New York 10032USA
- Resource Type
- Journal article
- Publication Details
- Journal of virology, Vol.70(7), pp.4299-4310
- DOI
- 10.1128/JVI.70.7.4299-4310.1996
- PMID
- 8676452
- PMCID
- PMC190362
- ISSN
- 0022-538X
- eISSN
- 1098-5514
- Language
- English
- Date published
- 07/1996
- Academic Unit
- Anatomy and Cell Biology; Internal Medicine
- Record Identifier
- 9984025562502771
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