Structural insights into the activity and regulation of human Josephin-2.

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 Å 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

SUBMITTER: Grasty KC 

PROVIDER: S-EPMC7337049 | biostudies-literature | 2019 Jul-Sep

REPOSITORIES: biostudies-literature