8SRD

Cryo-EM structure of TRPM2 chanzyme in the presence of Magnesium and ADP-ribose, open state

8SRD の概要

• エントリーDOI: 10.2210/pdb8srd/pdb
• EMDBエントリー: 40727 40868 40879
• 分子名称: TRPM2 chanzyme, ADENOSINE-5-DIPHOSPHORIBOSE, MAGNESIUM ION, ... (5 entities in total)
• 機能のキーワード: trpm2 chanzyme, channel-enzyme, membrane protein
• 由来する生物種: Salpingoeca rosetta
• タンパク質・核酸の鎖数: 4
• 化学式量合計: 682634.72

構造登録者

Huang, Y.,Kumar, S.,Lu, W.,Du, J. (登録日: 2023-05-05, 公開日: 2024-05-15, 最終更新日: 2024-10-23)

主引用文献

Huang, Y.,Kumar, S.,Lee, J.,Lu, W.,Du, J.
Coupling enzymatic activity and gating in an ancient TRPM chanzyme and its molecular evolution.
Nat.Struct.Mol.Biol., 2024

PubMed Abstract: Channel enzymes represent a class of ion channels with enzymatic activity directly or indirectly linked to their channel function. We investigated a TRPM2 chanzyme from choanoflagellates that integrates two seemingly incompatible functions into a single peptide: a channel module activated by ADP-ribose with high open probability and an enzyme module (NUDT9-H domain) consuming ADP-ribose at a remarkably slow rate. Using time-resolved cryogenic-electron microscopy, we captured a complete series of structural snapshots of gating and catalytic cycles, revealing the coupling mechanism between channel gating and enzymatic activity. The slow kinetics of the NUDT9-H enzyme module confers a self-regulatory mechanism: ADPR binding triggers NUDT9-H tetramerization, promoting channel opening, while subsequent hydrolysis reduces local ADPR, inducing channel closure. We further demonstrated how the NUDT9-H domain has evolved from a structurally semi-independent ADP-ribose hydrolase module in early species to a fully integrated component of a gating ring essential for channel activation in advanced species.

PubMed: 38773335
DOI: 10.1038/s41594-024-01316-4

実験手法

ELECTRON MICROSCOPY (2.91 Å)