title: "Depupylation" of prokaryotic ubiquitin-like protein from mycobacterial proteasome substrates.
abstract: 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.
authors: Department of Microbiology, New York University School of Medicine, New York, NY 10016, USA.
authors: Kristin E
authors: KE
authors: Burns
authors: Francisca A
authors: FA
authors: Cerda-Maira
authors: Tao
authors: T
authors: Wang
authors: Huilin
authors: H
authors: Li
authors: William R
authors: WR
authors: Bishai
authors: K Heran
authors: KH
authors: Darwin
mesh_terms: D001426:Bacterial Proteins / Q000235:genetics / Q000378:metabolism*; D009169:Mycobacterium tuberculosis / Q000235:genetics / Q000378:metabolism*; D046988:Proteasome Endopeptidase Complex / Q000235:genetics / Q000378:metabolism*; D014452:Ubiquitins / Q000235:genetics / Q000378:metabolism*
chemical_list: D001426:Bacterial Proteins; C533288:Pup protein, Mycobacterium tuberculosis; D014452:Ubiquitins; D046988:Proteasome Endopeptidase Complex