2Y5B

Structure of USP21 in complex with linear diubiquitin-aldehyde

Summary for 2Y5B

• Entry DOI: 10.2210/pdb2y5b/pdb
• Descriptor: UBIQUITIN CARBOXYL-TERMINAL HYDROLASE 21, UBIQUITIN, ZINC ION, ... (5 entities in total)
• Functional Keywords: protein binding-hydrolase complex, ubiquitin, ubiquitin specific protease, usp, nedd8, isg15, cell signaling, protein binding/hydrolase
• Biological source: HOMO SAPIENS (HUMAN); More
• Cellular location: Cytoplasm: Q9UK80; Ubiquitin: Cytoplasm (By similarity): P0CG47
• Total number of polymer chains: 4
• Total formula weight: 119174.21

Authors

Ye, Y.,Akutsu, M.,Reyes-Turcu, F.,Enchev, R.I.,Wilkinson, K.D.,Komander, D. (deposition date: 2011-01-12, release date: 2012-01-25, Last modification date: 2023-12-20)

Primary citation

Ye, Y.,Akutsu, M.,Reyes-Turcu, F.,Enchev, R.I.,Wilkinson, K.D.,Komander, D.
Polyubiquitin Binding and Cross-Reactivity in the Usp Domain Deubiquitinase Usp21.
Embo Rep., 12:350-, 2011

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.

PubMed: 21399617
DOI: 10.1038/EMBOR.2011.17

Experimental method

X-RAY DIFFRACTION (2.7 Å)