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-Structure paper
タイトル | Structures and gating mechanism of human TRPM2. |
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ジャーナル・号・ページ | Science, Vol. 362, Issue 6421, Year 2018 |
掲載日 | 2018年12月21日 |
著者 | Longfei Wang / Tian-Min Fu / Yiming Zhou / Shiyu Xia / Anna Greka / Hao Wu / |
PubMed 要旨 | 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 ...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. |
リンク | Science / PubMed:30467180 / PubMed Central |
手法 | EM (単粒子) |
解像度 | 3.6 - 6.36 Å |
構造データ | |
化合物 | ChemComp-CA: |
由来 |
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キーワード | MEMBRANE PROTEIN (膜タンパク質) / Channel / TRPM2 / TRP / ADPR (ADPリボース) / ADP-ribose (ADPリボース) / NUDT9H / NUDT9 / calcium (カルシウム) / ion channel (イオンチャネル) |