6MJ2

Human TRPM2 ion channel in a calcium- and ADPR-bound state

6MJ2 の概要

• エントリーDOI: 10.2210/pdb6mj2/pdb
• 関連するPDBエントリー: 6MIX 6MIZ 6MJ2
• EMDBエントリー: 9132 9133 9134
• 分子名称: Transient receptor potential cation channel subfamily M member 2, CALCIUM ION (2 entities in total)
• 機能のキーワード: channel, membrane protein, trpm2, trp, adpr, adp-ribose, nudt9h, nudt9, calcium, ion channel
• 由来する生物種: Homo sapiens (Human)
• タンパク質・核酸の鎖数: 4
• 化学式量合計: 685825.06

構造登録者

Wang, L.,Fu, T.M.,Xia, S.,Wu, H. (登録日: 2018-09-20, 公開日: 2018-12-12, 最終更新日: 2024-10-09)

主引用文献

Wang, L.,Fu, T.M.,Zhou, Y.,Xia, S.,Greka, A.,Wu, H.
Structures and gating mechanism of human TRPM2.
Science, 362:-, 2018

PubMed Abstract: Transient receptor potential (TRP) melastatin 2 (TRPM2) is a cation channel associated with numerous diseases. It has a C-terminal NUDT9 homology (NUDT9H) domain responsible for binding adenosine diphosphate (ADP)-ribose (ADPR), and both ADPR and calcium (Ca) are required for TRPM2 activation. Here we report cryo-electron microscopy structures of human TRPM2 alone, with ADPR, and with ADPR and Ca NUDT9H forms both intra- and intersubunit interactions with the N-terminal TRPM homology region (MHR1/2/3) in the apo state but undergoes conformational changes upon ADPR binding, resulting in rotation of MHR1/2 and disruption of the intersubunit interaction. The binding of Ca further engages transmembrane helices and the conserved TRP helix to cause conformational changes at the MHR arm and the lower gating pore to potentiate channel opening. These findings explain the molecular mechanism of concerted TRPM2 gating by ADPR and Ca and provide insights into the gating mechanism of other TRP channels.

PubMed: 30467180
DOI: 10.1126/science.aav4809

実験手法

ELECTRON MICROSCOPY (6.36 Å)