2AYO

Structure of USP14 bound to ubquitin aldehyde

Summary for 2AYO

• Entry DOI: 10.2210/pdb2ayo/pdb
• Related: 2AYN
• Descriptor: Ubiquitin carboxyl-terminal hydrolase 14, Ubiquitin (2 entities in total)
• Functional Keywords: deubiquitinating enzyme, dub, usp14, proteasome, enzyme mechanism, hydrolase
• Biological source: Homo sapiens (human); More
• Cellular location: Cytoplasm: P54578
• Total number of polymer chains: 2
• Total formula weight: 54771.21

Authors

Hu, M.,Li, P.,Jeffrey, P.D.,Shi, Y. (deposition date: 2005-09-07, release date: 2005-10-18, Last modification date: 2023-11-15)

Primary citation

Hu, M.,Li, P.,Song, L.,Jeffrey, P.D.,Chenova, T.A.,Wilkinson, K.D.,Cohen, R.E.,Shi, Y.
Structure and mechanisms of the proteasome-associated deubiquitinating enzyme USP14.
Embo J., 24:3747-3756, 2005

PubMed Abstract: The ubiquitin-specific processing protease (UBP) family of deubiquitinating enzymes plays an essential role in numerous cellular processes. Mammalian USP14 (Ubp6 in yeast) is unique among known UBP enzymes in that it is activated catalytically upon specific association with the 26S proteasome. Here, we report the crystal structures of the 45-kDa catalytic domain of USP14 in isolation and in a complex with ubiquitin aldehyde, which reveal distinct structural features. In the absence of ubiquitin binding, the catalytic cleft leading to the active site of USP14 is blocked by two surface loops. Binding by ubiquitin induces a significant conformational change that translocates the two surface loops thereby allowing access of the ubiquitin C-terminus to the active site. These structural observations, in conjunction with biochemical characterization, identify important regulatory mechanisms for USP14.

PubMed: 16211010
DOI: 10.1038/sj.emboj.7600832

Experimental method

X-RAY DIFFRACTION (3.5 Å)