"Depupylation" of Prokaryotic Ubiquitin-like Protein from Mycobacterial Proteasome Substrates

Journal Article · Fri Sep 10 04:00:00 EDT 2010 · Molecular Cell

DOI:https://doi.org/10.1016/j.molcel.2010.07.019· OSTI ID:1040565

Burns, K E; Li, H; Cerda-Maira, F A; Wang, T; Bishai, W R; Darwin, K H

Ubiquitin (Ub) provides the recognition and specificity required to deliver proteins to the eukaryotic proteasome for destruction. Prokaryotic ubiquitin-like protein (Pup) is functionally analogous to Ub in Mycobacterium tuberculosis (Mtb), as it dooms proteins to the Mtb proteasome. Studies suggest that Pup and Ub do not share similar mechanisms of activation and conjugation to target proteins. Dop (deamidase of Pup; Mtb Rv2112c/MT2172) deamidates the C-terminal glutamine of Pup to glutamate, preparing it for ligation to target proteins by proteasome accessory factor A (PafA). While studies have shed light on the conjugation of Pup to proteins, it was not known if Pup could be removed from substrates in a manner analogous to the deconjugation of Ub from eukaryotic proteins. Here, we show that Mycobacteria have a depupylase activity provided by Dop. The discovery of a depupylase strengthens the parallels between the Pup- and Ub-tagging systems of prokaryotes and eukaryotes, respectively.

• Research Organization: BROOKHAVEN NATIONAL LABORATORY (BNL)
• Sponsoring Organization: NATIONAL INSTITUTE OF HEALTH
• DOE Contract Number: AC02-98CH10886
• OSTI ID: 1040565
• Report Number(s): BNL--93983-2011-JA; 400412000
• Journal Information: Molecular Cell, Journal Name: Molecular Cell Journal Issue: 5 Vol. 39; ISSN 1097-2765
• Country of Publication: United States
• Language: English

Related Subjects

59 BASIC BIOLOGICAL SCIENCES
60 APPLIED LIFE SCIENCES
GLUTAMINE
MYCOBACTERIUM TUBERCULOSIS
PROTEINS
SPECIFICITY
SUBSTRATES
TARGETS