SAMPyling proteins in archaea

Abstract

For some time, post-translational small protein modifications were found only in eukaryotes; much later, such modifications were identified in some species of bacteria. The recent discovery of ubiquitin-like proteins that form polymeric chains and covalently modify proteins in archaea finally closes the evolutionary gap among the domains of life.

Fig. 1. Comparison of the eukaryotic and proposed prokaryotic Ub/Ubl-proteasome systems

(A) Eukaryotic Ub is encoded by four different loci in yeast (33) and is processed by Ub specific proteases that expose a C-terminal GlyGly motif. The C-terminus is the site of adenylation by an E1 enzyme, which via a series of transthioesterification reactions passes Ub to E2 and E3 enzymes. E3 enzymes are numerous (>600 in humans) (1) and determine which proteins are to be ubiquitylated. Ub is recognized by proteins in the regulatory cap of the 26S proteasome and is removed by deubiquitylases (DUBs) prior to destruction of the target substrate. (B) The bacterial Pup conjugation system uses enzymes unrelated to those in the eukaryotic Ub pathway. Pup is synthesized with a C-terminal Gln, which is deamidated by Dop. PafA catalyzes the ligation of Pup to substrates, presumably by a phosphorylated Pup intermediate. Pup is recognized by the Mycobacterial proteasome assocated ATPase, Mpa. It is not know if Pup is removed prior to degradation by a depupylase (DPUP). (C) Proposed H. volcanii SAMP-proteasome pathway. MoeB, a homologue of eukaryotic E1 activating enzymes, may be the E1 for SAMP1 and/or SAMP2. Homologues of eukaryotic E2 or E3 enzymes have not been identified in H. volcanni thus the conjugation of SAMPs to substrates remains to be determined. Furthermore, it is not known if “desampylation” occurs, although H. volcanii encodes two putative JAMM proteases. PAN: proteasome activating nucleotidase is a homologue of proteasome associated ATPases.

Fig. 2. Sequence relationship between archaeal, bacterial and eukaryotic β-grasp proteins

Neighbor-joining dendrogram visualizing the evolutionary relationship between the β-grasp proteome of Haloferax volcanii (Hv), Escherichia coli (Ec), and M. tuberculosis (Mt). Eukaryotic Urm1-like proteins from human (Hs) and budding yeast (Sc) are included for reference. The proteins can be classified into three major subfamilies groups: ThiS-like (red), SAMP-like (green) and MoaD/Urm1-like (blue).