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Related Experiment Videos

Domain swapping of CD4 upon dimerization.

Yves-Henri Sanejouand1

  • 1Laboratoire de Physique, Ecole Normale Supérieure, 46 allées d'Italie, 69364 Lyon Cédex 07, France. Yves-Henri.Sanejouand@ens-lyon.fr

Proteins
|August 25, 2004
PubMed
Summary

CD4 protein dimers form via 3D domain swapping, involving a disulfide bond that influences HIV infection. This mechanism explains how antibodies block HIV by disrupting dimer formation.

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Area of Science:

  • Structural Biology
  • Virology
  • Immunology

Background:

  • The Cys130-Cys159 disulfide bond in monomeric CD4 is crucial for forming CD4 dimers on cell surfaces, impacting HIV infection permissiveness.
  • This disulfide bond is buried within the monomer, necessitating a significant conformational change for exchange.

Purpose of the Study:

  • To investigate the conformational change enabling disulfide exchange in CD4 monomers.
  • To propose 3D domain swapping as the mechanism for CD4 dimer formation and its implications for HIV interaction.

Main Methods:

  • Utilized standard optimization techniques, validated with the CD2 case, to model CD4 conformational changes.
  • Analyzed the structural consequences of 3D domain swapping on disulfide bond formation between CD4 monomers.

Main Results:

  • 3D domain swapping, with loop E-F as the hinge, is identified as a likely mechanism for CD4 conformational change.
  • Domain swapping results in disulfide bonds between Cys130 of one monomer and Cys159 of another, forming CD4 dimers.
  • The proposed dimer configuration places the MT151 antibody epitope in a position to interfere with dimer formation.

Conclusions:

  • 3D domain swapping is a plausible mechanism for CD4 disulfide-bonded dimer formation.
  • This mechanism provides insight into how antibodies like MT151 can inhibit HIV infection by blocking CD4 dimerization.

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