3T9L

Structure of N-terminal DUSP-UBL domains of human USP15

Summary for 3T9L

• Entry DOI: 10.2210/pdb3t9l/pdb
• Related: 1W6V
• Descriptor: Ubiquitin carboxyl-terminal hydrolase 15, SULFATE ION (3 entities in total)
• Functional Keywords: domain present in ubiquitin specific proteases (dusp), ubiquitin-like domain (ubl), hydrolase, protease, deubiquitinating enzyme
• Biological source: Homo sapiens (human)
• Total number of polymer chains: 1
• Total formula weight: 26938.32

Authors

Harper, S.,Besong, T.M.D.,Emsley, J.,Scott, D.J.,Dreveny, I. (deposition date: 2011-08-03, release date: 2011-09-28, Last modification date: 2023-09-13)

Primary citation

Harper, S.,Besong, T.M.,Emsley, J.,Scott, D.J.,Dreveny, I.
Structure of the USP15 N-Terminal Domains: A beta-Hairpin Mediates Close Association between the DUSP and UBL Domains
Biochemistry, 50:7995-8004, 2011

PubMed Abstract: Ubiquitin specific protease 15 (USP15) functions in COP9 signalosome mediated regulation of protein degradation and cellular signaling through catalyzing the ubiquitin deconjugation reaction of a discrete number of substrates. It influences the stability of adenomatous polyposis coli, IκBα, caspase-3, and the human papillomavirus type 16 E6. USP15 forms a subfamily with USP4 and USP11 related through a shared presence of N-terminal "domain present in ubiquitin specific proteases" (DUSP) and "ubiquitin-like" (UBL) domains (DU subfamily). Here we report the 1.5 Å resolution crystal structure of the human USP15 N-terminal domains revealing a 80 Å elongated arrangement with the DU domains aligned in tandem. This architecture is generated through formation of a defined interface that is dominated by an intervening β-hairpin structure (DU finger) that engages in an intricate hydrogen-bonding network between the domains. The UBL domain is closely related to ubiquitin among β-grasp folds but is characterized by the presence of longer loop regions and different surface characteristics, indicating that this domain is unlikely to act as ubiquitin mimic. Comparison with the related murine USP4 DUSP-UBL crystal structure reveals that the main DU interdomain contacts are conserved. Analytical ultracentrifugation, small-angle X-ray scattering, and gel filtration experiments revealed that USP15 DU is monomeric in solution. Our data provide a framework to advance study of the structure and function of the DU subfamily.

PubMed: 21848306
DOI: 10.1021/bi200726e

Experimental method

X-RAY DIFFRACTION (1.5 Å)