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-Structure paper
タイトル | Structural basis of the activation of TRPV5 channels by long-chain acyl-Coenzyme-A. |
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ジャーナル・号・ページ | Nat Commun, Vol. 14, Issue 1, Page 5883, Year 2023 |
掲載日 | 2023年9月21日 |
著者 | Bo-Hyun Lee / José J De Jesús Pérez / Vera Moiseenkova-Bell / Tibor Rohacs / |
PubMed 要旨 | Long-chain acyl-coenzyme A (LC-CoA) is a crucial metabolic intermediate that plays important cellular regulatory roles, including activation and inhibition of ion channels. The structural basis of ...Long-chain acyl-coenzyme A (LC-CoA) is a crucial metabolic intermediate that plays important cellular regulatory roles, including activation and inhibition of ion channels. The structural basis of ion channel regulation by LC-CoA is not known. Transient receptor potential vanilloid 5 and 6 (TRPV5 and TRPV6) are epithelial calcium-selective ion channels. Here, we demonstrate that LC-CoA activates TRPV5 and TRPV6 in inside-out patches, and both exogenously supplied and endogenously produced LC-CoA can substitute for the natural ligand phosphatidylinositol 4,5-bisphosphate (PI(4,5)P) in maintaining channel activity in intact cells. Utilizing cryo-electron microscopy, we determined the structure of LC-CoA-bound TRPV5, revealing an open configuration with LC-CoA occupying the same binding site as PI(4,5)P in previous studies. This is consistent with our finding that PI(4,5)P could not further activate the channels in the presence of LC-CoA. Our data provide molecular insights into ion channel regulation by a metabolic signaling molecule. |
リンク | Nat Commun / PubMed:37735536 / PubMed Central |
手法 | EM (単粒子) |
解像度 | 3.09 - 3.5 Å |
構造データ | EMDB-29049, PDB-8ffo: EMDB-29085, PDB-8fhh: EMDB-29086, PDB-8fhi: |
化合物 | ChemComp-ERG: ChemComp-CPL: ChemComp-PIO: ChemComp-POV: ChemComp-3VV: |
由来 |
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キーワード | MEMBRANE PROTEIN / TRPV5 / TRP Channel / PI(4 / 5)P2 / oleoyl coenzyme A / Closed state / Open state |