8FHH

Wildtype rabbit TRPV5 in nanodiscs in the presence of oleoyl coenzyme A, Closed stated

Summary for 8FHH

• Entry DOI: 10.2210/pdb8fhh/pdb
• EMDB information: 29085
• Descriptor: Transient receptor potential cation channel subfamily V member 5, (2S)-3-(hexadecanoyloxy)-2-[(9Z)-octadec-9-enoyloxy]propyl 2-(trimethylammonio)ethyl phosphate, ERGOSTEROL (3 entities in total)
• Functional Keywords: trpv5, trp channel, oleoyl coenzyme a, closed state, membrane protein
• Biological source: Oryctolagus cuniculus (rabbit)
• Total number of polymer chains: 4
• Total formula weight: 341351.83

Authors

De Jesus-Perez, J.J.,Moiseenkova-Bell, V.Y. (deposition date: 2022-12-14, release date: 2023-11-01)

Primary citation

Lee, B.H.,De Jesus Perez, J.J.,Moiseenkova-Bell, V.,Rohacs, T.
Structural basis of the activation of TRPV5 channels by long-chain acyl-Coenzyme-A.
Nat Commun, 14:5883-5883, 2023

PubMed 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)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.

PubMed: 37735536
DOI: 10.1038/s41467-023-41577-z

Experimental method

ELECTRON MICROSCOPY (3.09 Å)