Suppression of retroviral MA deletions by the amino-terminal membrane-binding domain of p60src

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Retroviral Scanning: Mapping MLV Integration Sites to Define Cell-specific Regulatory Regions
10:10

Retroviral Scanning: Mapping MLV Integration Sites to Define Cell-specific Regulatory Regions

Published on: May 28, 2017

J W Wills1, R C Craven, R A Weldon

  • 1Department of Biochemistry and Molecular Biology, Louisiana State University Medical Center, Shreveport 71130.

Journal of Virology
|July 11, 1991
PubMed

Insights

Rous sarcoma virus Gag protein deletions block particle formation. Fusing a specific amino-terminal sequence from p60src rescues this defect, suggesting a novel membrane targeting mechanism for retroviral budding.

Area of Science:

  • Molecular Virology
  • Cell Biology
  • Protein Trafficking

Background:

  • The mechanism directing retroviral Gag proteins to the plasma membrane for particle formation (budding) is not fully understood.
  • The matrix (MA) domain at the amino terminus of Gag proteins is hypothesized to be critical for this process.

Purpose of the Study:

  • To investigate the role of the MA domain in Rous sarcoma virus (RSV) Gag protein localization and particle formation.
  • To identify signals that can overcome defects caused by MA domain deletions.

Main Methods:

  • Generated Rous sarcoma virus Gag proteins with small deletions in the MA domain.
  • Assessed particle formation by expressing mutant and chimeric Gag proteins.
  • Investigated the effect of fusing specific peptide sequences, including the myristylated amino terminus of p60src, to mutant Gag proteins.

Main Results:

  • Small deletions in the RSV Gag MA domain completely abolished particle formation.
  • These defects were rescued by coexpression with wild-type Gag proteins, indicating localized structural damage.
  • Fusion of the myristylated amino terminus of p60src, but not other myristylated peptides, suppressed the MA deletion phenotype, restoring particle formation.

Conclusions:

  • The MA domain is essential for Rous sarcoma virus Gag protein targeting and particle formation.
  • Myristoylation alone is insufficient for membrane targeting; specific protein sequences are required.
  • The amino terminus of p60src may divert Gag proteins to a specific receptor, overriding the MA domain's normal function in assembly.

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