2i50
From Proteopedia
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Solution Structure of Ubp-M Znf-UBP domain
Overview
The BUZ/Znf-UBP domain is a distinct ubiquitin-binding module found in the, cytoplasmic deacetylase HDAC6, the E3 ubiquitin ligase BRAP2/IMP, and a, subfamily of deubiquitinating enzymes. Here, we report the solution, structure of the BUZ domain of Ubp-M, a ubiquitin-specific protease, and, its interaction with ubiquitin. Unlike the BUZ domain from isopeptidase T, (isoT) that contains a single zinc finger, the Ubp-M BUZ domain features, three zinc-binding sites consisting of 12 residues. These zinc ligands, form a pair of cross-braced ring fingers encapsulated within a third zinc, finger in the primary structure. In contrast to isoT, which can form an, N-terminal loop swapped dimer in the crystal state, the formation of, additional zinc fingers in the Ubp-M BUZ domain restricts its N-terminal, loop to intra-domain interactions. The ubiquitin-binding site of the Ubp-M, BUZ domain is mapped to the highly conserved, concave surface formed by, the alpha 3 helix and the central beta-sheet. We further show that this, site binds to the C-terminal tail of free ubiquitin, and corresponding, peptides display essentially the same binding affinities as full-length, ubiquitin does for the Ubp-M BUZ domain. However, modification of the, G76(Ub) carboxylate group either by a peptide or isopeptide bond abolishes, BUZ-domain interaction. The unique ubiquitin-recognition mode of the BUZ, domain family suggests that they may function as "sensors" of free, ubiquitin in cells to achieve regulatory roles in many aspects of, ubiquitin-dependent processes.
About this Structure
2I50 is a Single protein structure of sequence from Homo sapiens with as ligand. Active as Ubiquitin thiolesterase, with EC number 3.1.2.15 Full crystallographic information is available from OCA.
Reference
Solution structure of the Ubp-M BUZ domain, a highly specific protein module that recognizes the C-terminal tail of free ubiquitin., Pai MT, Tzeng SR, Kovacs JJ, Keaton MA, Li SS, Yao TP, Zhou P, J Mol Biol. 2007 Jul 6;370(2):290-302. Epub 2007 Apr 12. PMID:17512543
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