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Visualization of HIV-1 Gag Binding to Giant Unilamellar Vesicle (GUV) Membranes
Published on: July 28, 2016
Interactions between HIV-1 Gag molecules in solution: an inositol phosphate-mediated switch
Siddhartha A K Datta1, Zhuojun Zhao, Patrick K Clark
1HIV Drug Resistance Program, National Cancer Institute-Frederick, Frederick, MD 21702, USA.
Journal of Molecular Biology
|November 14, 2006
Summary
Inositol hexakisphosphate (IP6) binding to the human immunodeficiency virus type 1 (HIV-1) Gag protein alters its assembly dynamics. IP6 binding promotes Gag trimerization, essential for proper virus-like particle (VLP) formation.
Area of Science:
- Virology
- Structural Biology
- Biochemistry
Background:
- Retrovirus particle assembly relies on the Gag polyprotein.
- Recombinant HIV-1 Gag protein forms virus-like particles (VLPs) in vitro, but with abnormal curvature.
- Inositol phosphates can correct VLP assembly defects.
Purpose of the Study:
- To investigate the binding of inositol hexakisphosphate (IP6) to HIV-1 Gag.
- To determine how IP6 affects Gag-Gag interactions and VLP assembly.
Main Methods:
- In vitro assembly of recombinant HIV-1 Gag protein.
- Analysis of Gag protein interactions in solution using IP6.
- Mutagenesis of the Gag dimer interface.
Main Results:
- IP6 binds to basic regions at both ends of the Gag protein.
- IP6 shifts Gag equilibrium from monomer-dimer to monomer-trimer.
- A mutation at the Gag dimer interface prevents trimerization even with IP6, indicating its importance.
Conclusions:
- IP6 binding induces a conformational change in Gag, promoting trimerization.
- The Gag dimer interface is crucial for IP6-mediated trimerization.
- Gag likely undergoes a significant conformational change during assembly, folding in solution before forming the viral structure.
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