Structural highlights
Function
UBP34_HUMAN Ubiquitin hydrolase that can remove conjugated ubiquitin from AXIN1 and AXIN2, thereby acting as a regulator of Wnt signaling pathway. Acts as an activator of the Wnt signaling pathway downstream of the beta-catenin destruction complex by deubiquitinating and stabilizing AXIN1 and AXIN2, leading to promote nuclear accumulation of AXIN1 and AXIN2 and positively regulate beta-catenin (CTNBB1)-mediated transcription. Recognizes and hydrolyzes the peptide bond at the C-terminal Gly of ubiquitin. Involved in the processing of poly-ubiquitin precursors as well as that of ubiquitinated proteins.[1]
Publication Abstract from PubMed
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.
Structural Insights into the Catalytic Mechanism and Ubiquitin Recognition of USP34.,Xu G, Su H, Lu L, Liu X, Zhao L, Tang B, Ming Z J Mol Biol. 2022 May 16;434(13):167634. doi: 10.1016/j.jmb.2022.167634. PMID:35588869[2]
From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine.
References
- ↑ Lui TT, Lacroix C, Ahmed SM, Goldenberg SJ, Leach CA, Daulat AM, Angers S. The ubiquitin-specific protease USP34 regulates axin stability and Wnt/β-catenin signaling. Mol Cell Biol. 2011 May;31(10):2053-65. PMID:21383061 doi:10.1128/MCB.01094-10
- ↑ 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. 2022 Jul 15;434(13):167634. PMID:35588869 doi:10.1016/j.jmb.2022.167634
