8FFO

Cryo-EM structure of wildtype rabbit TRPV5 with PI(4,5)P2 in nanodiscs

Summary for 8FFO

• Entry DOI: 10.2210/pdb8ffo/pdb
• EMDB information: 29049
• Descriptor: Transient receptor potential cation channel subfamily V member 5, ERGOSTEROL, 1-PALMITOYL-2-LINOLEOYL-SN-GLYCERO-3-PHOSPHOCHOLINE, ... (4 entities in total)
• Functional Keywords: trpv5, trp channel, pi(4, 5)p2, membrane protein
• Biological source: Oryctolagus cuniculus (rabbit)
• Total number of polymer chains: 4
• Total formula weight: 353426.75

Authors

De Jesus-Perez, J.J.,Moiseenkova-Bell, V.Y. (deposition date: 2022-12-09, 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 (3.5 Å)