Pearce MJ, Mintseris J, Ferreyra J, Gygi SP, Darwin KH.
Ubiquitin-Like Protein Involved in the Proteasome Pathway of Mycobacterium tuberculosis. Science. 2008 Oct 2. [Epub ahead of print] PMID: 18832610

This study provides compelling evidence for a novel ubiquitin-like conjugation system that targets proteins for proteasomal degradation in prokaryotes.

By using a two-hybrid screen, Pearce et al. identified a ubiquitin-like protein, termed pup, that is covalently attached to proteasome substrates in Mycobacterium tuberculosis. In contrast to ubiquitination, pup is thought to utilize a de-amidated glutamine residue at the C-terminus for isopeptide bond formation with the substrate lysine. Moreover, proteasome accessory factor A (PafA) was shown to be required for pup conjugation. This discovery may result in the development of powerful new pharmacological strategies for the treatment of infectious diseases, in particular tuberculosis.

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