Ubiquitin-like protein involved in the proteasome pathway of Mycobacterium tuberculosis.
The protein modifier ubiquitin is a signal for proteasome-mediated degradation in eukaryotes. Proteasome-bearing prokaryotes have been thought to degrade proteins via a ubiquitin-independent pathway. We have identified a prokaryotic ubiquitin-like protein, Pup (Rv2111c), which was specifically conjugated to proteasome substrates in the pathogen Mycobacterium tuberculosis. Pupylation occurred on lysines and required proteasome accessory factor A (PafA). In a pafA mutant, pupylated proteins were absent and substrates accumulated, thereby connecting pupylation with degradation. Although analogous to ubiquitylation, pupylation appears to proceed by a different chemistry. Thus, like eukaryotes, bacteria may use a small-protein modifier to control protein stability.
Pearce
Michael J
MJ
Department of Microbiology, New York University School of Medicine, New York, NY 10016, USA.
Mintseris
Julian
J
Ferreyra
Jessica
J
Gygi
Steven P
SP
Darwin
K Heran
KH
D000251:Adenosine Triphosphatases / Q000235:genetics / Q000378:metabolism*; D020816:Amino Acid Motifs; D001426:Bacterial Proteins / Q000737:chemistry / Q000235:genetics / Q000302:isolation & purification / Q000378:metabolism*; D018698:Glutamic Acid / Q000378:metabolism; D005973:Glutamine / Q000378:metabolism; D005998:Glycine / Q000378:metabolism; D008239:Lysine / Q000378:metabolism; D013058:Mass Spectrometry; D008969:Molecular Sequence Data; D009154:Mutation; D020102:Mycobacterium smegmatis / Q000378:metabolism; D009169:Mycobacterium tuberculosis / Q000235:genetics / Q000378:metabolism*; D046988:Proteasome Endopeptidase Complex / Q000378:metabolism*; D011993:Recombinant Fusion Proteins / Q000737:chemistry / Q000378:metabolism; D054875:Ubiquitination; D014452:Ubiquitins / Q000737:chemistry / Q000235:genetics / Q000302:isolation & purification / Q000378:metabolism*
D001426:Bacterial Proteins; C533288:Pup protein, Mycobacterium tuberculosis; D011993:Recombinant Fusion Proteins; D014452:Ubiquitins; D005973:Glutamine; D018698:Glutamic Acid; D046988:Proteasome Endopeptidase Complex; D000251:Adenosine Triphosphatases; C479920:Mpa protein, Mycobacterium tuberculosis; D008239:Lysine; D005998:Glycine