Publication Abstract from PubMed
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.
Polyubiquitin binding and cross-reactivity in the USP domain deubiquitinase USP21.,Ye Y, Akutsu M, Reyes-Turcu F, Enchev RI, Wilkinson KD, Komander D EMBO Rep. 2011 Apr;12(4):350-7. Epub 2011 Mar 11. PMID:21399617[1]
From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine.
