2I50

Solution Structure of Ubp-M Znf-UBP domain

Summary for 2I50

• Entry DOI: 10.2210/pdb2i50/pdb
• NMR Information: BMRB: 7298
• Descriptor: Ubiquitin carboxyl-terminal hydrolase 16, ZINC ION (2 entities in total)
• Functional Keywords: alpha/beta zinc-finger, ring-finger, znf-ubp, metalloprotein, ubiquitin-binding protein, usp, ubiquitin, hydrolase
• Biological source: Homo sapiens (human)
• Cellular location: Nucleus (Probable): Q9Y5T5
• Total number of polymer chains: 1
• Total formula weight: 14677.64

Authors

Pai, M.-T. (deposition date: 2006-08-23, release date: 2007-08-07, Last modification date: 2024-05-29)

Primary citation

Pai, M.T.,Tzeng, S.R.,Kovacs, J.J.,Keaton, M.A.,Li, S.S.,Yao, T.P.,Zhou, P.
Solution structure of the Ubp-M BUZ domain, a highly specific protein module that recognizes the C-terminal tail of free ubiquitin.
J.Mol.Biol., 370:290-302, 2007

PubMed Abstract: 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.

PubMed: 17512543
DOI: 10.1016/j.jmb.2007.04.015

Experimental method

SOLUTION NMR