8FFL

Wildtype rat TRPV2 in nanodiscs bound to RR

Summary for 8FFL

• Entry DOI: 10.2210/pdb8ffl/pdb
• EMDB information: 29046
• Descriptor: Transient receptor potential cation channel subfamily V member 2, 1,2-DIDECANOYL-SN-GLYCERO-3-PHOSPHOETHANOLAMINE (2 entities in total)
• Functional Keywords: trpv2, trpv5, trp channel, ruthenium red, membrane protein
• Biological source: Rattus norvegicus (Norway rat)
• Total number of polymer chains: 4
• Total formula weight: 349286.09

Authors

Pumroy, R.A.,Protopopova, A.D.,Rocereta, J.A.,De Jesus-Perez, J.J.,Fluck, E.C.,Moiseenkova-Bell, V.Y. (deposition date: 2022-12-09, release date: 2024-02-07, Last modification date: 2024-02-21)

Primary citation

Pumroy, R.A.,De Jesus-Perez, J.J.,Protopopova, A.D.,Rocereta, J.A.,Fluck, E.C.,Fricke, T.,Lee, B.H.,Rohacs, T.,Leffler, A.,Moiseenkova-Bell, V.
Molecular details of ruthenium red pore block in TRPV channels.
Embo Rep., 25:506-523, 2024

PubMed Abstract: Transient receptor potential vanilloid (TRPV) channels play a critical role in calcium homeostasis, pain sensation, immunological response, and cancer progression. TRPV channels are blocked by ruthenium red (RR), a universal pore blocker for a wide array of cation channels. Here we use cryo-electron microscopy to reveal the molecular details of RR block in TRPV2 and TRPV5, members of the two TRPV subfamilies. In TRPV2 activated by 2-aminoethoxydiphenyl borate, RR is tightly coordinated in the open selectivity filter, blocking ion flow and preventing channel inactivation. In TRPV5 activated by phosphatidylinositol 4,5-bisphosphate, RR blocks the selectivity filter and closes the lower gate through an interaction with polar residues in the pore vestibule. Together, our results provide a detailed understanding of TRPV subfamily pore block, the dynamic nature of the selectivity filter and allosteric communication between the selectivity filter and lower gate.

PubMed: 38225355
DOI: 10.1038/s44319-023-00050-0

Experimental method

ELECTRON MICROSCOPY (3.47 Å)