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Identification of Nucleolar Factors During HIV-1 Replication Through Rev Immunoprecipitation and Mass Spectrometry
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Identification of Nucleolar Factors During HIV-1 Replication Through Rev Immunoprecipitation and Mass Spectrometry

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Mutations that mimic phosphorylation of the HIV-1 matrix protein do not perturb the myristyl switch

Jamil S Saad1, Andrew Kim, Ruba H Ghanam

  • 1Howard Hughes Medical Institute and Department of Chemistry and Biochemistry, University of Maryland, Baltimore County, Baltimore, Maryland 21250, USA.

Protein Science : a Publication of the Protein Society
|July 28, 2007
PubMed

Insights

Phosphorylation of HIV-1 matrix protein (MA) does not affect its membrane binding or myristyl switch. This suggests phosphorylation unlikely influences HIV-1 trafficking within cells.

Area of Science:

  • Molecular Virology
  • Cell Biology
  • Structural Biology

Background:

  • The HIV-1 matrix protein (MA) is crucial for viral assembly, directing Gag polyproteins to the plasma membrane.
  • MA utilizes a phosphatidylinositol-4,5-bisphosphate (PIP(2))-dependent myristyl switch for membrane targeting.
  • MA's role in nuclear trafficking and potential regulation by phosphorylation remain controversial.

Purpose of the Study:

  • To investigate the impact of mimicking MA phosphorylation on the myristyl switch mechanism.
  • To assess how phosphorylation-mimicking mutations affect MA's interaction with lipid bilayers.
  • To determine if MA phosphorylation influences HIV-1 intracellular trafficking.

Main Methods:

  • Construction and analysis of HIV-1 MA mutants with Ser-to-Asp substitutions to mimic phosphorylation.
  • Assays to evaluate the PIP(2)- and concentration-dependent myristyl switch equilibrium.
  • Liposome binding experiments to measure the affinity of wild-type and mutant MA proteins.

Main Results:

  • None of the tested MA phosphorylation-mimicking mutations altered the myristyl switch equilibrium.
  • Mutant MA proteins showed only slightly reduced liposome binding affinity compared to native MA.
  • Myristylated MA mutants exhibited substantially greater liposome binding affinity than unmyristylated MA.

Conclusions:

  • Phosphorylation is unlikely to be a significant regulator of the HIV-1 MA myristyl switch or membrane binding.
  • The myristyl switch mechanism is robust and not significantly perturbed by mimicking phosphorylation.
  • Findings challenge the hypothesis that MA phosphorylation plays a major role in membrane-mediated intracellular trafficking.

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