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Assessment of Immunologically Relevant Dynamic Tertiary Structural Features of the HIV-1 V3 Loop Crown R2 Sequence by ab initio Folding
Published on: September 15, 2010
Is the V3 loop involved in HIV binding to CD4?
Monica Dettin1, Pasquale Ferranti, Claudia Scarinci
1Department of Chemical Process Engineering, University of Padova, 35131-Padova, Italy. monica.dettin@unipd.it
Insights
Researchers identified a specific interaction between HIV-MN-gp120 V3 loop and the CD4 Ig-CDR3-like region. This finding advances understanding of HIV entry and aids in developing new antiviral therapies.
Area of Science:
- Virology
- Immunology
- Structural Biology
Background:
- Human immunodeficiency virus (HIV) entry into host cells depends on interactions between the viral envelope glycoprotein gp120 and cellular receptors CD4 and chemokine receptors.
- The gp120 binding site on CD4 has been localized to the Ig-CDR2-like region of the CD4 first domain.
- A second region, the Ig-CDR3-like region of CD4, is implicated in gp120-CD4 interactions, but the corresponding gp120 binding partner was previously unidentified.
Purpose of the Study:
- To identify the specific region on the HIV-MN-gp120 V3 loop that interacts with the CD4 Ig-CDR3-like region.
- To elucidate the molecular mechanisms underlying HIV-1 entry and cell penetration.
Main Methods:
- Photoaffinity labeling experiments were employed to investigate molecular interactions.
- Peptide mapping of the HIV-MN-gp120 V3 loop, specifically the (307-330)m region, was performed.
Main Results:
- A peptide corresponding to the (307-330)m region of the HIV-MN-gp120 V3 loop was found to bind to a specific sequence within the CD4 Ig-CDR3-like region.
- This interaction provides the missing link between the gp120 V3 loop and the CD4 receptor.
Conclusions:
- The study successfully identified a critical binding interaction between a V3 loop peptide of HIV-MN-gp120 and the CD4 Ig-CDR3-like region.
- These findings enhance the understanding of the complex HIV-1 entry pathway.
- The identified interaction may serve as a target for the development of novel therapeutic agents against HIV infection.
Abstract:
The entry of the human immunodeficiency virus into cells requires the interaction of the viral envelope glycoprotein gp120 with CD4 and a chemokine receptor. The gp120 binding site has been previously mapped to the Ig-CDR2-like region of CD4 first domain. A second area of this domain (Ig-CDR3-like region) is involved in gp120-CD4 interactions, but its gp120 counterpart remained so far unknown. Using a photoaffinity labeling experiment, we demonstrate that a peptide, mapping the (307-330)m region of HIV-MN-gp120 V3 loop, binds a sequence including a part of the Ig-CDR3-like region. These results may contribute to explain the complex mechanism of human immunodeficiency virus penetration, helping the development of new therapeutic agents.
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