Molecular analysis of the prokaryotic ubiquitin-like protein (Pup) conjugation pathway in Mycobacterium tuberculosis

Francisca A. Cerda-Maira, Michael J. Pearce, Michele Fuortes, William R. Bishai, Stevan R. Hubbard, K. Heran Darwin

Research output: Contribution to journalArticle

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.

Original languageEnglish (US)
Pages (from-to)1123-1135
Number of pages13
JournalMolecular Microbiology
Volume77
Issue number5
DOIs
StatePublished - Sep 1 2010

ASJC Scopus subject areas

  • Microbiology
  • Molecular Biology

Fingerprint Dive into the research topics of 'Molecular analysis of the prokaryotic ubiquitin-like protein (Pup) conjugation pathway in Mycobacterium tuberculosis'. Together they form a unique fingerprint.

  • Cite this