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Binding of SGTA to Rpn13 selectively modulates protein quality control

Pawel Leznicki1, Jelena Korac-Prlic2, Katarzyna Kliza3

  • 1Faculty of Life Sciences, University of Manchester, Oxford Road, Manchester M13 9PT, UK.

Journal of Cell Science
|July 15, 2015
PubMed

Insights

The cytosolic factor SGTA binds Rpn13, a proteasome component, to regulate the degradation of mislocalized membrane proteins (MLPs). This interaction is crucial for controlling MLP levels via the 26S proteasome.

Area of Science:

  • Cell Biology
  • Protein Degradation
  • Molecular Mechanisms

Background:

  • Rpn13 is a ubiquitin receptor in the 26S proteasome, essential for substrate capture.
  • SGTA is a cytosolic factor involved in the quality control of mislocalized membrane proteins (MLPs).

Purpose of the Study:

  • To investigate the interaction between Rpn13 and SGTA.
  • To elucidate the role of SGTA-Rpn13 interaction in regulating MLP proteasomal degradation.

Main Methods:

  • Co-immunoprecipitation assays to confirm protein-protein interactions.
  • Analysis of steady-state MLP levels upon overexpression of SGTA or Rpn13 mutants.
  • Site-directed mutagenesis to disrupt the SGTA-Rpn13 binding interface.

Main Results:

  • The C-terminal region of Rpn13 directly binds to the tetratricopeptide repeat (TPR) domain of SGTA.
  • Overexpression of SGTA increases steady-state MLP levels, dependent on Rpn13 interaction.
  • Disruption of SGTA-Rpn13 binding via Rpn13 mutants or SGTA mutations reduces MLP levels.

Conclusions:

  • SGTA regulates MLP access to the 26S proteasome through its interaction with Rpn13.
  • A protein quality control pathway involving SGTA and the BAG6 complex operates at the 19S proteasome regulatory particle.
  • SGTA-Rpn13 binding may modulate substrate degradation, potentially allowing escape from proteasomal degradation.
Keywords:
Bag6Mislocalised proteinsProteasomesProtein degradationTPRUbiquitylation

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