Protein Family Models

This family consists of several short bacterial proteins formely known as (DUF797). It was recently shown that Mycobacterium tuberculosis contains a small protein, Pup (Rv2111c), that is covalently conjugated to the e-NH2 groups of lysines on several target proteins (pupylation) such as the malonyl CoA acyl carrier protein (FabD) [2]. Pupylation of FabD was shown to result in its recruitment to the mycobacterial proteasome and subsequent degradation analogous to eukaryotic ubiquitin-conjugated proteins. Searches recovered Pup orthologs in all major actinobacteria lineages including the basal bifidobacteria and also sporadically in certain other bacterial lineages. [1] The Pup proteins were all between 50-90 residues in length and a multiple alignment shows that they all contain a conserved motif with a G [EQ] signature at the C-terminus. Thus, all of them are suitable for conjugation via the terminal glutamate or the deamidated glutamine (as shown in the case of the Mycobacterium Pup [1]). The conserved globular core of Pup is predicted to form a bihelical unit with the extreme C-terminal 6-7 residues forming a tail in the extended conformation. Thus, Pup is structurally unrelated to the ubiquitin fold and has convergently evolved the function of protein modifier. [1]. 18980670. Unraveling the biochemistry and provenance of pupylation: a prokaryotic analog of ubiquitination. Iyer LM, Burroughs AM, Aravind L;. Biol Direct. 2008;3:45. [2]. 18832610. Ubiquitin-like protein involved in the proteasome pathway of Mycobacterium tuberculosis. Pearce MJ, Mintseris J, Ferreyra J, Gygi SP, Darwin KH;. Science. 2008;322:1104-1107. (from Pfam)

Date:

2024-10-16

Members of this protein family are Pup, a small protein whose ligation to target proteins steers them toward degradation. This protein family occurs in a number of bacteria, especially Actinobacteria such as Mycobacterium tuberculosis, that possess an archeal-type proteasome. All members of this protein family known during model construction end with the C-terminal motif [FY][VI]QKGG[QE]. Ligation is thought to occur between the C-terminal COOH of Pup and an epsilon-amino group of a Lys on the target protein. The N-terminal half of this protein is poorly conserved and not represented in the seed alignment.

Date:

2024-06-26

ubiquitin-like protein Pup is a protein modifier that is covalently attached to lysine residues of substrate proteins, thereby targeting them for proteasomal degradation

Date:

2020-03-06