4WLQ

Crystal structure of mUCH37-hRPN13 CTD complex

Summary for 4WLQ

• Entry DOI: 10.2210/pdb4wlq/pdb
• Related: 4WLP 4WLR
• Descriptor: Ubiquitin carboxyl-terminal hydrolase isozyme L5, Proteasomal ubiquitin receptor ADRM1 (2 entities in total)
• Functional Keywords: uch37 rpn13 proteasome ino80 dub, protein binding
• Biological source: Mus musculus (Mouse); More
• Total number of polymer chains: 2
• Total formula weight: 47924.45

Authors

Hemmis, C.W.,Hill, C.P.,VanderLinden, R.,Whitby, F.G. (deposition date: 2014-10-07, release date: 2015-03-04, Last modification date: 2023-12-27)

Primary citation

VanderLinden, R.T.,Hemmis, C.W.,Schmitt, B.,Ndoja, A.,Whitby, F.G.,Robinson, H.,Cohen, R.E.,Yao, T.,Hill, C.P.
Structural Basis for the Activation and Inhibition of the UCH37 Deubiquitylase.
Mol.Cell, 57:901-911, 2015

PubMed Abstract: The UCH37 deubiquitylase functions in two large and very different complexes, the 26S proteasome and the INO80 chromatin remodeler. We have performed biochemical characterization and determined crystal structures of UCH37 in complexes with RPN13 and NFRKB, which mediate its recruitment to the proteasome and INO80, respectively. RPN13 and NFRKB make similar contacts to the UCH37 C-terminal domain but quite different contacts to the catalytic UCH domain. RPN13 can activate UCH37 by disrupting dimerization, although physiologically relevant activation likely results from stabilization of a surface competent for ubiquitin binding and modulation of the active-site crossover loop. In contrast, NFRKB inhibits UCH37 by blocking the ubiquitin-binding site and by disrupting the enzyme active site. These findings reveal remarkable commonality in mechanisms of recruitment, yet very different mechanisms of regulating enzyme activity, and provide a foundation for understanding the roles of UCH37 in the unrelated proteasome and INO80 complexes.

PubMed: 25702872
DOI: 10.1016/j.molcel.2015.01.016

Experimental method

X-RAY DIFFRACTION (2.85 Å)