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Updated: Aug 10, 2026
Determination of Molecular Structures of HIV Envelope Glycoproteins using Cryo-Electron Tomography and Automated Sub-tomogram Averaging
Published on: December 1, 2011
Towards a structure of the HIV-1 envelope glycoprotein gp120: an immunochemical approach
J P Moore1, B A Jameson, Q J Sattentau
1Aaron Diamond AIDS Research Center, New York University School of Medicine, New York 10016.
Insights
Researchers mapped the HIV-1 gp120 surface using antibodies to understand its structure. This antibody mapping reveals how different parts of the glycoprotein interact, aiding in modeling its complex three-dimensional form.
Area of Science:
- Virology
- Structural Biology
- Immunology
Background:
- The Human Immunodeficiency Virus type 1 (HIV-1) surface glycoprotein gp120 is crucial for initial virus-cell fusion via CD4 binding.
- Extensive glycosylation of gp120 hinders structural determination using traditional crystallographic methods.
Purpose of the Study:
- To elucidate the structure of HIV-1 gp120 by mapping its surface topology using antibodies.
- To identify regions of gp120 accessible on the native molecule versus those exposed after denaturation.
- To characterize epitopes recognized by antibodies binding to complex surface structures and understand inter-domain interactions.
Main Methods:
- Antibody mapping of the gp120 surface to identify accessible and internal regions.
- Epitope mapping to define antibody binding sites on complex surface structures.
- Analysis of mutation effects on antibody binding to assess inter-domain communication.
Main Results:
- Identification of surface-accessible and internally exposed regions of gp120.
- Characterization of epitopes involving segments from different gp120 domains.
- Demonstration of how mutations in one domain impact antibody binding to epitopes on other domains, indicating functional inter-domain relationships.
Conclusions:
- Antibody mapping provides a viable approach to understanding the structure of the heavily glycosylated gp120.
- Inter-domain interactions within gp120 are significant and can be probed through antibody binding studies.
- These findings facilitate the modeling of individual gp120 domains and their interactions in the folded protein structure.
Abstract:
The HIV-1 surface glycoprotein gp120 binds CD4 in the initial state of virus-cell fusion. The extensive glycosylation of gp120 has thus far precluded definition of its structure by crystallographic methods. As an initial approach to a gp120 structure, the surface topology was mapped using antibodies. First, the regions of gp120 that are accessible on the surface of the native molecule, and those that are internal but exposed after denaturation, are identified. Second, epitopes for antibodies that recognize complex surface structures comprising segments of different domains are identified. Third, we define how mutations in one domain of gp120 influence the binding of antibodies to defined epitopes on other domains. These latter approaches enable us to start to understand the inter-domain interactions that contribute to the overall structure of the gp120 molecule. Information from these studies is being used to model the structures of individual gp120 domains, and the way in which these interact in the folded protein.
