Structural basis of the activation of TRPV5 channels by long-chain acyl-Coenzyme-Aopen access
- Authors
- Lee, Bo-Hyun; De Jesús Pérez, José J.; Moiseenkova-Bell, Vera; Rohacs, Tibor
- Issue Date
- Sep-2023
- Publisher
- Nature Research
- Citation
- Nature Communications, v.14, no.1
- Indexed
- SCIE
SCOPUS
- Journal Title
- Nature Communications
- Volume
- 14
- Number
- 1
- URI
- https://scholarworks.gnu.ac.kr/handle/sw.gnu/68024
- DOI
- 10.1038/s41467-023-41577-z
- ISSN
- 2041-1723
- Abstract
- 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)P2) 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)P2 in previous studies. This is consistent with our finding that PI(4,5)P2 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. © 2023, Springer Nature Limited.
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