8DDU

cryo-EM structure of TRPM3 ion channel in the presence of PIP2, state3

Summary for 8DDU

• Entry DOI: 10.2210/pdb8ddu/pdb
• Related: 8DDQ 8DDR 8DDS 8DDT
• EMDB information: 27342
• Descriptor: Transient receptor potential cation channel, subfamily M, member 3, Unidentified segment at the N-terminus of TRPM3, 1,2-DIACYL-GLYCEROL-3-SN-PHOSPHATE, ... (6 entities in total)
• Functional Keywords: trpm3, ion channel, pip2, membrane protein
• Biological source: Mus musculus (house mouse); More
• Total number of polymer chains: 8
• Total formula weight: 645142.33

Authors

Zhao, C.,MacKinnon, R. (deposition date: 2022-06-19, release date: 2022-11-02, Last modification date: 2024-06-12)

Primary citation

Zhao, C.,MacKinnon, R.
Structural and functional analyses of a GPCR-inhibited ion channel TRPM3.
Neuron, 111:81-, 2023

PubMed Abstract: G-protein coupled receptors (GPCRs) govern the physiological response to stimuli by modulating the activity of downstream effectors, including ion channels. TRPM3 is an ion channel inhibited by GPCRs through direct interaction with G protein (Gβγ) released upon their activation. This GPCR-TRPM3 signaling pathway contributes to the analgesic effect of morphine. Here, we characterized Gβγ inhibition of TRPM3 using electrophysiology and single particle cryo-electron microscopy (cryo-EM). From electrophysiology, we obtained a half inhibition constant (IC50) of ∼240 nM. Using cryo-EM, we determined structures of mouse TRPM3 expressed in human cells with and without Gβγ and with and without PIP, a lipid required for TRPM3 activity, at resolutions of 2.7-4.7 Å. Gβγ-TRPM3 interfaces vary depending on PIP occupancy; however, in all cases, Gβγ appears loosely attached to TRPM3. The IC50 in electrophysiology experiments raises the possibility that additional unknown factors may stabilize the TRPM3-Gβγ complex.

PubMed: 36283409
DOI: 10.1016/j.neuron.2022.10.002

Experimental method

ELECTRON MICROSCOPY (3 Å)