The regulatory significance of tag recycling in the mycobacterial Pup-proteasome system

FEBS J. 2017 Jun;284(12):1804-1814. doi: 10.1111/febs.14086. Epub 2017 May 18.

Abstract

Pup, a ubiquitin analog, tags proteins for degradation by the bacterial proteasome. As an intracellular proteolytic system, the Pup-proteasome system (PPS) must be carefully regulated to prevent excessive protein degradation. Currently, those factors underlying PPS regulation remain poorly understood. Here, experimental analysis combined with theoretical modeling of in vivo protein pupylation revealed how the basic PPS design allows stable and controlled protein pupylation. Specifically, the recycling of Pup when targets are degraded allows the PPS to maintain steady-state levels of protein pupylation and degradation at a rate limited by proteasome function, and at a pupylome level limited by Pup concentrations. This design allows the Pup-ligase, a highly promiscuous enzyme, to act in a controlled manner without causing damage, and the PPS to be effectively tuned to control protein degradation. This study thus provides understanding of how the inherent design of an intracellular proteolytic system serves crucial regulatory purposes.

Keywords: Dop; PafA; Pup; proteasome; proteolysis.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Bacterial Proteins / metabolism*
  • Mycobacterium Infections, Nontuberculous / metabolism*
  • Mycobacterium Infections, Nontuberculous / microbiology
  • Mycobacterium smegmatis / metabolism*
  • Proteasome Endopeptidase Complex / metabolism*
  • Protein Processing, Post-Translational*
  • Proteolysis
  • Ubiquitin / metabolism*
  • Ubiquitins / metabolism*

Substances

  • Bacterial Proteins
  • Pup protein, Mycobacterium tuberculosis
  • Ubiquitin
  • Ubiquitins
  • Proteasome Endopeptidase Complex

Associated data

  • figshare/10.6084/m9.figshare.5001905