7W3U

USP34 catalytic domain in complex with UbPA

Summary for 7W3U

• Entry DOI: 10.2210/pdb7w3u/pdb
• Descriptor: Ubiquitin carboxyl-terminal hydrolase 34, Polyubiquitin-B, ZINC ION, ... (4 entities in total)
• Functional Keywords: usp34 in complex, hydrolase
• Biological source: Homo sapiens (human); More
• Total number of polymer chains: 6
• Total formula weight: 160620.26

Authors

Xu, G.L.,Ming, Z.H. (deposition date: 2021-11-26, release date: 2022-06-01, Last modification date: 2024-04-24)

Primary citation

Xu, G.,Su, H.,Lu, L.,Liu, X.,Zhao, L.,Tang, B.,Ming, Z.
Structural Insights into the Catalytic Mechanism and Ubiquitin Recognition of USP34.
J.Mol.Biol., 434:167634-167634, 2022

PubMed Abstract: Ubiquitination, an important posttranslational modification, participates in virtually all aspects of cellular functions and is reversed by deubiquitinating enzymes (DUBs). Ubiquitin-specific protease 34 (USP34) plays an essential role in cancer, neurodegenerative diseases, and osteogenesis. Despite its functional importance, how USP34 recognizes ubiquitin and catalyzes deubiquitination remains structurally uncharacterized. Here, we report the crystal structures of the USP34 catalytic domain in free state and after binding with ubiquitin. In the free state, USP34 adopts an inactive conformation, which contains a misaligned catalytic histidine in the triad. Comparison of USP34 structures before and after ubiquitin binding reveals a structural basis for ubiquitin recognition and elucidates a mechanism by which the catalytic triad is realigned. Transition from an open inactive state to a relatively closed active state is coupled to a process by which the "fingertips" of USP34 intimately grip ubiquitin, and this has not been reported before. Our structural and biochemical analyses provide important insights into the catalytic mechanism and ubiquitin recognition of USP34.

PubMed: 35588869
DOI: 10.1016/j.jmb.2022.167634

Experimental method

X-RAY DIFFRACTION (3.13 Å)