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4UEL

UCH-L5 in complex with ubiquitin-propargyl bound to the RPN13 DEUBAD domain

Summary for 4UEL
Entry DOI10.2210/pdb4uel/pdb
Related4UEM
DescriptorUBIQUITIN CARBOXYL-TERMINAL HYDROLASE ISOZYME L5, POLYUBIQUITIN-B, PROTEASOMAL UBIQUITIN RECEPTOR ADRM1, ... (4 entities in total)
Functional Keywordshydrolase, deubiquitinating enzyme, dub, uch37, uchl5, proteasome, adrm1, rpn13, deubad, uch, ubiquitin-propargyl
Biological sourceHOMO SAPIENS (HUMAN)
More
Total number of polymer chains3
Total formula weight59359.46
Authors
Sahtoe, D.D.,Van Dijk, W.J.,El Oualid, F.,Ekkebus, R.,Ovaa, H.,Sixma, T.K. (deposition date: 2014-12-18, release date: 2015-03-04, Last modification date: 2024-10-23)
Primary citationSahtoe, D.D.,Van Dijk, W.J.,El Oualid, F.,Ekkebus, R.,Ovaa, H.,Sixma, T.K.
Mechanism of Uch-L5 Activation and Inhibition by Deubad Domains in Rpn13 and Ino80G.
Mol.Cell, 57:887-, 2015
Cited by
PubMed Abstract: Deubiquitinating enzymes (DUBs) control vital processes in eukaryotes by hydrolyzing ubiquitin adducts. Their activities are tightly regulated, but the mechanisms remain elusive. In particular, the DUB UCH-L5 can be either activated or inhibited by conserved regulatory proteins RPN13 and INO80G, respectively. Here we show how the DEUBAD domain in RPN13 activates UCH-L5 by positioning its C-terminal ULD domain and crossover loop to promote substrate binding and catalysis. The related DEUBAD domain in INO80G inhibits UCH-L5 by exploiting similar structural elements in UCH-L5 to promote a radically different conformation, and employs molecular mimicry to block ubiquitin docking. In this process, large conformational changes create small but highly specific interfaces that mediate activity modulation of UCH-L5 by altering the affinity for substrates. Our results establish how related domains can exploit enzyme conformational plasticity to allosterically regulate DUB activity. These allosteric sites may present novel insights for pharmaceutical intervention in DUB activity.
PubMed: 25702870
DOI: 10.1016/J.MOLCEL.2014.12.039
PDB entries with the same primary citation
Experimental method
X-RAY DIFFRACTION (2.3 Å)
Structure validation

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