Unraveling the biochemistry and provenance of pupylation: a prokaryotic analog of ubiquitinationReportar como inadecuado




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Biology Direct

, 3:45

First Online: 03 November 2008Received: 28 October 2008Accepted: 03 November 2008

Abstract

Recently Mycobacterium tuberculosis was shown to possess a novel protein modification, in which a small protein Pup is conjugated to the epsilon-amino groups of lysines in target proteins. Analogous to ubiquitin modification in eukaryotes, this remarkable modification recruits proteins for degradation via archaeal-type proteasomes found in mycobacteria and allied actinobacteria. While a mycobacterial protein named PafA was found to be required for this conjugation reaction, its biochemical mechanism has not been elucidated. Using sensitive sequence profile comparison methods we establish that the PafA family proteins are related to the γ-glutamyl-cysteine synthetase and glutamine synthetase. Hence, we predict that PafA is the Pup ligase, which catalyzes the ATP-dependent ligation of the terminal γ-carboxylate of glutamate to lysines, similar to the above enzymes. We further discovered that an ortholog of the eukaryotic PAC2 e.g. cg2106 is often present in the vicinity of the actinobacterial Pup-proteasome gene neighborhoods and is likely to represent the ancestral proteasomal chaperone. Pup-conjugation is sporadically present outside the actinobacteria in certain lineages, such as verrucomicrobia, nitrospirae, deltaproteobacteria and planctomycetes, and in the latter two lineages it might modify membrane proteins.

ReviewersThis article was reviewed by M. Madan Babu and Andrei Osterman

Electronic supplementary materialThe online version of this article doi:10.1186-1745-6150-3-45 contains supplementary material, which is available to authorized users.

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Autor: Lakshminarayan M Iyer - AM Burroughs - L Aravind

Fuente: https://link.springer.com/article/10.1186/1745-6150-3-45







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