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Conformational Evaluation of HIV-1 Trimeric Envelope Glycoproteins Using a Cell-based ELISA Assay
Published on: September 14, 2014
Peptide mimic of the HIV envelope gp120-gp41 interface
Sunghwan Kim1, Hong-Bo Pang, Michael S Kay
1Department of Biochemistry, University of Utah School of Medicine, 15 North Medical Drive East, Room 4100, Salt Lake City, UT 84112-5650, USA.
Journal of Molecular Biology
|January 8, 2008
Summary
Researchers modeled the human immunodeficiency virus envelope glycoprotein (Env) interface. They found that gp120 binding to gp41 prevents viral fusion until coreceptor interaction occurs, offering insights into HIV entry mechanisms.
Area of Science:
- Virology
- Structural Biology
- Biochemistry
Background:
- Human immunodeficiency virus (HIV) entry relies on the envelope glycoprotein (Env), comprising gp120 and gp41 subunits.
- Env undergoes conformational changes upon binding CD4 and coreceptors, driving viral membrane fusion.
- The precise interactions at the gp120-gp41 interface in the prefusion state remain unclear.
Purpose of the Study:
- To investigate the structural and functional interactions within the prefusogenic gp120-gp41 complex.
- To elucidate how Env conformational changes are communicated between gp120 and gp41.
- To understand the mechanism preventing premature trimer-of-hairpins formation.
Main Methods:
- Development of a biochemical model system mimicking the prefusogenic gp120-gp41 interface.
- Analysis of interactions between gp41 fragments (disulfide bond loop, C-peptide) and gp120 (C5 region).
Main Results:
- A gp41 fragment containing the disulfide bond loop and C-peptide binds the gp120 C5 region.
- This interaction is incompatible with the formation of the trimer-of-hairpins structure.
- A model is proposed where gp120 sequesters the gp41 C-peptide, inhibiting fusion.
Conclusions:
- The gp120-gp41 interface plays a critical role in regulating HIV Env conformational changes.
- gp120 actively prevents gp41 trimer-of-hairpins formation in the prefusogenic state.
- The developed model system facilitates further studies on HIV fusion and Env structure.
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