6HEH
Structure of the catalytic domain of USP28 (insertion deleted)
Summary for 6HEH
| Entry DOI | 10.2210/pdb6heh/pdb |
| Descriptor | Ubiquitin carboxyl-terminal hydrolase 28,Ubiquitin carboxyl-terminal hydrolase 28, 1,2-ETHANEDIOL, CHLORIDE ION, ... (4 entities in total) |
| Functional Keywords | ubiquitin, usp, ubiquitin-specific protease, dub, deubiquitinase, protease, isopeptidase, usp28, hydrolase |
| Biological source | Homo sapiens (Human) More |
| Total number of polymer chains | 1 |
| Total formula weight | 44684.21 |
| Authors | Gersch, M.,Komander, D. (deposition date: 2018-08-20, release date: 2019-03-27, Last modification date: 2024-01-17) |
| Primary citation | Gersch, M.,Wagstaff, J.L.,Toms, A.V.,Graves, B.,Freund, S.M.V.,Komander, D. Distinct USP25 and USP28 Oligomerization States Regulate Deubiquitinating Activity. Mol.Cell, 74:436-, 2019 Cited by PubMed Abstract: The evolutionarily related deubiquitinating enzymes (DUBs) USP25 and USP28 comprise an identical overall domain architecture but are functionally non-redundant: USP28 stabilizes c-MYC and other nuclear proteins, and USP25 regulates inflammatory TRAF signaling. We here compare molecular features of USP25 and USP28. Active enzymes form distinctively shaped dimers, with a dimerizing insertion spatially separating independently active catalytic domains. In USP25, but not USP28, two dimers can form an autoinhibited tetramer, where a USP25-specific, conserved insertion sequence blocks ubiquitin binding. In full-length enzymes, a C-terminal domain with a previously unknown fold has no impact on oligomerization, but N-terminal regions affect the dimer-tetramer equilibrium in vitro. We confirm oligomeric states of USP25 and USP28 in cells and show that modulating oligomerization affects substrate stabilization in accordance with in vitro activity data. Our work highlights how regions outside of the catalytic domain enable a conceptually intriguing interplay of DUB oligomerization and activity. PubMed: 30926242DOI: 10.1016/j.molcel.2019.02.030 PDB entries with the same primary citation |
| Experimental method | X-RAY DIFFRACTION (2.26 Å) |
Structure validation
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