9QEP

Cryo-EM structure of O-GlcNAcase from Trichoplax Adhaerens

9QEP の概要

• エントリーDOI: 10.2210/pdb9qep/pdb
• EMDBエントリー: 53082
• 分子名称: O-GlcNAcase (1 entity in total)
• 機能のキーワード: gh84 hydrolase, hydrolase
• 由来する生物種: Trichoplax adhaerens
• タンパク質・核酸の鎖数: 2
• 化学式量合計: 168189.77

構造登録者

Basse Hansen, S.,Bartual, S.G.,Yuan, H.,Raimi, O.G.,Gorelik, A.,Ferenbach, A.T.,Lytje, K.,Pedersen, J.S.,Drace, T.,Boesen, T.,van Aalten, D.M.F. (登録日: 2025-03-10, 公開日: 2025-09-17, 最終更新日: 2025-10-15)

主引用文献

Hansen, S.B.,Bartual, S.G.,Yuan, H.,Raimi, O.G.,Gorelik, A.,Ferenbach, A.T.,Lytje, K.,Pedersen, J.S.,Drace, T.,Boesen, T.,van Aalten, D.M.F.
Multi-domain O-GlcNAcase structures reveal allosteric regulatory mechanisms.
Nat Commun, 16:8828-8828, 2025

PubMed Abstract: Nucleocytoplasmic protein O-GlcNAcylation is a dynamic modification catalysed by O-GlcNAc transferase (OGT) and reversed by O-GlcNAc hydrolase (OGA), whose activities are regulated through largely unknown O-GlcNAc-dependent feedback mechanisms. OGA is a homodimeric, multi-domain enzyme containing a catalytic core and a pseudo-histone acetyltransferase (pHAT) domain. While a catalytic structure has been reported, the structure and function of the pHAT domain remain elusive. Here, we report a crystal structure of the Trichoplax adhaerens pHAT domain and cryo-EM data of the multi-domain T. adhaerens and human OGAs, complemented by biophysical analyses. Here, we show that the eukaryotic OGA pHAT domain forms catalytically incompetent, symmetric homodimers, projecting a partially conserved putative peptide-binding site. In solution, OGA exist as flexible multi-domain dimers, but catalytic core-pHAT linker interactions restrict pHAT positional range. In human OGA, pHAT movements remodel the active site environment through conformational changes in a flexible arm region. These findings reveal allosteric mechanisms through which the pHAT domain contributes to O-GlcNAc homeostasis.

PubMed: 41044083
DOI: 10.1038/s41467-025-63893-2

実験手法

ELECTRON MICROSCOPY (2.99 Å)