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-Structure paper
タイトル | Structural dynamics at cytosolic interprotomer interfaces control gating of a mammalian TRPM5 channel. |
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ジャーナル・号・ページ | Proc Natl Acad Sci U S A, Vol. 121, Issue 27, Page e2403333121, Year 2024 |
掲載日 | 2024年7月2日 |
著者 | Sebastian Karuppan / Lynn Goss Schrag / Caroline M Pastrano / Andrés Jara-Oseguera / Lejla Zubcevic / |
PubMed 要旨 | The transient receptor potential melastatin (TRPM) tetrameric cation channels are involved in a wide range of biological functions, from temperature sensing and taste transduction to regulation of ...The transient receptor potential melastatin (TRPM) tetrameric cation channels are involved in a wide range of biological functions, from temperature sensing and taste transduction to regulation of cardiac function, inflammatory pain, and insulin secretion. The structurally conserved TRPM cytoplasmic domains make up >70 % of the total protein. To investigate the mechanism by which the TRPM cytoplasmic domains contribute to gating, we employed electrophysiology and cryo-EM to study TRPM5-a channel that primarily relies on activation via intracellular Ca. Here, we show that activation of mammalian TRPM5 channels is strongly altered by Ca-dependent desensitization. Structures of rat TRPM5 identify a series of conformational transitions triggered by Ca binding, whereby formation and dissolution of cytoplasmic interprotomer interfaces appear to control activation and desensitization of the channel. This study shows the importance of the cytoplasmic assembly in TRPM5 channel function and sets the stage for future investigations of other members of the TRPM family. |
リンク | Proc Natl Acad Sci U S A / PubMed:38923985 / PubMed Central |
手法 | EM (単粒子) |
解像度 | 3.5 - 5.0 Å |
構造データ | EMDB-40574, PDB-8sl6: EMDB-40575, PDB-8sl8: EMDB-40576, PDB-8sla: EMDB-40577, PDB-8sle: EMDB-40578, PDB-8sli: EMDB-40579, PDB-8slp: EMDB-40580, PDB-8slq: EMDB-40581, PDB-8slw: EMDB-40592: Focused map of the cytoplasmic domains of rat TRPM5, conformation high-4 EMDB-40593: Focused map of the cytoplasmic domains of rat TRPM5, conformation high-3 EMDB-40595: Focused map of the cytoplasmic domains of rat TRPM5, conformation high-2 EMDB-40596: Focused map of the cytoplasmic domains of rat TRPM5, conformation high-1 EMDB-40597: Focused map of the cytoplasmic domains of rat TRPM5, conformation trace-3 EMDB-40599: Focused map of the cytoplasmic domains of rat TRPM5, conformation trace-2 EMDB-40600: Focused map of the cytoplasmic domains of rat TRPM5, conformation trace-1 |
化合物 | ChemComp-CA: |
由来 |
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キーワード | MEMBRANE PROTEIN / ion channel / Transient Receptor Potential / TRP / Transient Receptor Potential Melastatin 5 / TRPM5 / TRANSPORT PROTEIN |