7T38

Inactivated state of 2-APB and CBD-bound wildtype rat TRPV2 in nanodiscs

Summary for 7T38

• Entry DOI: 10.2210/pdb7t38/pdb
• EMDB information: 25650 25651
• Descriptor: Transient receptor potential cation channel subfamily V member 2 (1 entity in total)
• Functional Keywords: trp channel, ion channel, trpv, transport protein
• Biological source: Rattus norvegicus (Norway rat)
• Total number of polymer chains: 4
• Total formula weight: 347195.56

Authors

Pumroy, R.A.,Protopopova, A.D.,Gallo, P.N.,Moiseenkova-Bell, V.Y. (deposition date: 2021-12-07, release date: 2022-05-04, Last modification date: 2024-02-28)

Primary citation

Pumroy, R.A.,Protopopova, A.D.,Fricke, T.C.,Lange, I.U.,Haug, F.M.,Nguyen, P.T.,Gallo, P.N.,Sousa, B.B.,Bernardes, G.J.L.,Yarov-Yarovoy, V.,Leffler, A.,Moiseenkova-Bell, V.Y.
Structural insights into TRPV2 activation by small molecules.
Nat Commun, 13:2334-2334, 2022

PubMed Abstract: Transient receptor potential vanilloid 2 (TRPV2) is involved in many critical physiological and pathophysiological processes, making it a promising drug target. Here we present cryo-electron microscopy (cryo-EM) structures of rat TRPV2 in lipid nanodiscs activated by 2-aminoethoxydiphenyl borate (2-APB) and propose a TRPV2-specific 2-ABP binding site at the interface of S5 of one monomer and the S4-S5 linker of the adjacent monomer. In silico docking and electrophysiological studies confirm the key role of His521 and Arg539 in 2-APB activation of TRPV2. Additionally, electrophysiological experiments show that the combination of 2-APB and cannabidiol has a synergetic effect on TRPV2 activation, and cryo-EM structures demonstrate that both drugs were able to bind simultaneously. Together, our cryo-EM structures represent multiple functional states of the channel, providing a native picture of TRPV2 activation by small molecules and a structural framework for the development of TRPV2-specific activators.

PubMed: 35484159
DOI: 10.1038/s41467-022-30083-3

Experimental method

ELECTRON MICROSCOPY (3.8 Å)