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Related Experiment Videos

A zinc-binding region in Vif binds Cul5 and determines cullin selection.

Andrew Mehle1, Elaine R Thomas1, Kottampatty S Rajendran1

  • 1Department of Cancer Immunology and AIDS, Dana Farber Cancer Institute, Boston, Massachusetts 02115; Departments of Pathology, Harvard Medical School, Boston, Massachusetts 02115.

The Journal of Biological Chemistry
|April 26, 2006
PubMed
Summary

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Human immunodeficiency virus-1 (HIV-1) Vif protein uses a novel zinc-binding motif to selectively bind Cullin 5, facilitating the degradation of APOBEC3G and overcoming antiviral defenses. This interaction is crucial for viral replication.

Area of Science:

  • Virology
  • Molecular Biology
  • Structural Biology

Background:

  • Human immunodeficiency virus-1 (HIV-1) Vif protein counters host antiviral factors like APOBEC3G.
  • Vif targets APOBEC3G for degradation via a Cullin 5-ElonginB-ElonginC (Cul5-EloBC) E3 ligase complex.
  • The precise mechanism of Vif's selective recruitment of Cul5 remains unclear.

Purpose of the Study:

  • To elucidate the mechanism by which Vif selectively recruits Cul5.
  • To identify the specific Vif region and motif responsible for Cul5 interaction.
  • To understand how this interaction facilitates APOBEC3G degradation.

Main Methods:

  • Site-directed mutagenesis of Vif protein residues.
  • Zinc coordination assays.
  • Co-immunoprecipitation to assess protein-protein interactions (Vif-Cul5).

Related Experiment Videos

  • APOBEC3G degradation assays.

    • Main Results:

    • A novel Vif region (residues 100-142) upstream of the BC-box selectively binds Cul5 independently of EloC.
    • This region contains a conserved HCCH zinc coordination motif (His/Cys residues at 108, 114, 133, 139).
    • Mutations in the HCCH motif or conserved hydrophobic residues (Ile-120, Ala-123, Leu-124) disrupt zinc binding, Cul5 interaction, and APOBEC3G degradation.
    • Vif binds to the N-terminal cullin repeat of Cul5.

    Conclusions:

    • The HCCH zinc-binding motif in Vif represents a novel cullin interaction domain.
    • This domain mediates selective Vif-Cul5 binding, crucial for Vif's function.
    • The motif likely facilitates Vif-Cul5 interaction by positioning hydrophobic residues for direct contact with Cul5, enabling APOBEC3G ubiquitination and degradation.