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| Subject Categories: Proteins | Structural Biology |
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| The EMBO Journal
(2005) 24, 3747–3756, doi:10.1038/sj.emboj.7600832 Published online 6 October 2005 |
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| Structure and mechanisms of the proteasome-associated deubiquitinating enzyme USP14 |
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| Min Hu1, 4, Pingwei Li1, 4, Ling Song2, Philip D Jeffrey1, Tatiana A Chenova3, Keith D Wilkinson3, Robert E Cohen2 and Yigong Shi1 |
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1 Department of Molecular Biology, Lewis Thomas Laboratory, Princeton University, Princeton, NJ, USA 2 Department of Biochemistry, University of Iowa, Iowa City, IA, USA 3 Department of Biochemistry, Emory University School of Medicine, Atlanta, GA, USA To whom correspondence should be addressed Yigong Shi, Department of Molecular Biology, Lewis Thomas Laboratory, Princeton University, Princeton, NJ 08544, USA. Tel.: +1 609 258 6071; Fax: +1 609 258 6730; E-mail: yshi@molbio.princeton.edu 4 These authors contributed equally to this work Received 11 July 2005; Accepted 12 September 2005; Published online 6 October 2005. |
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| Abstract |
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| 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. |
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| Keywords: crystal structure, deubiquitination, deubiquitinating enzymes, mechanism, UBP |
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Top of page MORE ARTICLES LIKE THISThese links to content published by NPG are automatically generated NEWS AND VIEWSNature Structural & Molecular Biology News and Views (01 Dec 2006) Nature Cell Biology News and Views (01 Oct 2006) RESEARCHStructural basis for the specificity of ubiquitin C-terminal hydrolases The EMBO Journal Article (15 Jul 1999) |
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