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Journal article
Structural insights into the activity and regulation of human Josephin-2
JOURNAL OF STRUCTURAL BIOLOGY-X, v 3(C), pp 100011-100011
01 Jul 2019
PMID: 32647816
Featured in Collection : UN Sustainable Development Goals @ Drexel
Abstract
The MJD family of human deubiquitinating enzymes contains four members: Ataxin-3, the ataxin-3-like protein (AT3L), Josephin-1, and Josephin-2. All share a conserved catalytic unit known as the Josephin domain. Ataxin-3 and AT3L also contain extensive regulatory regions that modulate their functions, whereas Josephins-1 and -2 are substantially smaller, containing only the Josephin domain. To gain insight into how these minimal Josephins differ from their larger relatives, we determined the 2.3 angstrom X-ray crystal structure of human Josephin-2 and probed the enzyme's substrate specificity. Several large disordered loops are seen in the structure, suggesting a highly dynamic enzyme. Josephin-2 lacks several allosteric sites found in ataxin-3, but its structure suggests potential regulation via ubiquitination of a loop adjoining the active site. The enzyme preferentially recognizes substrates containing K11, K48, and K63 linkages, pointing toward a possible role in maintenance of protein quality control.
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Details
- Title
- Structural insights into the activity and regulation of human Josephin-2
- Creators
- Kimberly C. Grasty - Drexel UniversityStephen D. Weeks - Drexel UniversityPatrick J. Loll - Drexel University
- Publication Details
- JOURNAL OF STRUCTURAL BIOLOGY-X, v 3(C), pp 100011-100011
- Publisher
- Elsevier
- Number of pages
- 9
- Grant note
- R01GM079508 / National Institute of General Medical Sciences (NIGMS)/National Institutes of Health (NIH) R01NS065140 / NIH; United States Department of Health & Human Services; National Institutes of Health (NIH) - USA Office of Biological and Environmental Research of the US Department of Energy; United States Department of Energy (DOE) NIGMS of the NIH; United States Department of Health & Human Services; National Institutes of Health (NIH) - USA; NIH National Institute of General Medical Sciences (NIGMS) Office of Basic Energy Sciences of the US Department of Energy; United States Department of Energy (DOE)
- Resource Type
- Journal article
- Language
- English
- Academic Unit
- Biochemistry and Molecular Biology
- Web of Science ID
- WOS:000658507300003
- Scopus ID
- 2-s2.0-85072807948
- Other Identifier
- 991019168158604721
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- Collaboration types
- International collaboration
- Web of Science research areas
- Biochemistry & Molecular Biology
- Biophysics
- Cell Biology