Polyubiquitin binding and cross-reactivity in the USP domain deubiquitinase USP21.
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Ye Y, Akutsu M, Reyes-Turcu F, Enchev RI, Wilkinson KD, Komander D
Polyubiquitin binding and cross-reactivity in the USP domain deubiquitinase USP21.
EMBO Rep. 2011 Apr;12(4):350-7. doi: 10.1038/embor.2011.17. Epub 2011 Mar 11.
- PubMed ID
- 21399617 [ View in PubMed]
- Abstract
Modification of proteins by ubiquitin (Ub) and Ub-like (Ubl) modifiers regulates a variety of cellular functions. The ability of Ub to form chains of eight structurally and functionally distinct types adds further complexity to the system. Ub-specific proteases (USPs) hydrolyse polyUb chains, and some have been suggested to be cross-reactive with Ubl modifiers, such as neural precursor cell expressed, developmentally downregulated 8 (NEDD8) and interferon-stimulated gene 15 (ISG15). Here, we report that USP21 cleaves Ub polymers, and with reduced activity also targets ISG15, but is inactive against NEDD8. A crystal structure of USP21 in complex with linear diUb aldehyde shows how USP21 interacts with polyUb through a previously unidentified second Ub- and ISG15-binding surface on the USP domain core. We also rationalize the inability of USP21 to target NEDD8 and identify differences that allow USPs to distinguish between structurally related modifications.