Molecular analysis of the prokaryotic ubiquitin-like protein (Pup) conjugation pathway in Mycobacterium tuberculosis. Academic Article uri icon

Overview

abstract

  • Proteins targeted for degradation by the Mycobacterium proteasome are post-translationally tagged with prokaryotic ubiquitin-like protein (Pup), an intrinsically disordered protein of 64 residues. In a process termed 'pupylation', Pup is synthesized with a terminal glutamine, which is deamidated to glutamate by Dop (deamidase of Pup) prior to attachment to substrate lysines by proteasome accessory factor A (PafA). Importantly, PafA was previously shown to be essential to cause lethal infections by Mycobacterium tuberculosis (Mtb) in mice. In this study we show that Dop, like PafA, is required for the full virulence of Mtb. Additionally, we show that Dop is not only involved in the deamidation of Pup, but also needed to maintain wild-type steady state levels of pupylated proteins in Mtb. Finally, using structural models and site-directed mutagenesis our data suggest that Dop and PafA are members of the glutamine synthetase fold family of proteins.

publication date

  • September 1, 2010

Research

keywords

  • Amidohydrolases
  • Bacterial Proteins
  • Mycobacterium tuberculosis
  • Ubiquitins
  • Virulence Factors

Identity

PubMed Central ID

  • PMC2975802

Scopus Document Identifier

  • 77956162428

Digital Object Identifier (DOI)

  • 10.1111/j.1365-2958.2010.07276.x

PubMed ID

  • 20636328

Additional Document Info

volume

  • 77

issue

  • 5