Structure and Mechanisms of the Proteasome-associated Deubiquitinating Enzyme USP14

Journal Article · Sat Jan 01 04:00:00 EST 2005 · EMBO J.

DOI:https://doi.org/10.1038/sj.emboj.7600832· OSTI ID:913779

Hu, M; Li, P; Song, L; Jeffrey, P; Chernova, T; Wilkinson, K; Cohen, R; Shi, Y

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.

• Research Organization: Brookhaven National Laboratory (BNL) National Synchrotron Light Source
• Sponsoring Organization: Doe - Office Of Science
• DOE Contract Number: AC02-98CH10886
• OSTI ID: 913779
• Report Number(s): BNL--78347-2007-JA
• Journal Information: EMBO J., Journal Name: EMBO J. Journal Issue: 21 Vol. 24; ISSN EMJODG; ISSN 0261-4189
• Country of Publication: United States
• Language: English

Related Subjects

36 MATERIALS SCIENCE
CONFORMATIONAL CHANGES
CRYSTAL STRUCTURE
ENZYMES
PROCESSING
national synchrotron light source