8GVX

Cryo-EM structure of the human TRPC5 ion channel in complex with G alpha i3 subunits, class2

Summary for 8GVX

• Entry DOI: 10.2210/pdb8gvx/pdb
• Related: 7X6I
• EMDB information: 34301 34394 34396
• Descriptor: Short transient receptor potential channel 5, Guanine nucleotide-binding protein G(i) subunit alpha-3, PHOSPHATIDYLETHANOLAMINE, ... (8 entities in total)
• Functional Keywords: trp, transient receptor potential, metal transport
• Biological source: Homo sapiens (human); More
• Total number of polymer chains: 8
• Total formula weight: 535181.28

Authors

Won, J.,Jeong, H.,Lee, H.H. (deposition date: 2022-09-16, release date: 2023-05-24, Last modification date: 2024-11-20)

Primary citation

Won, J.,Kim, J.,Jeong, H.,Kim, J.,Feng, S.,Jeong, B.,Kwak, M.,Ko, J.,Im, W.,So, I.,Lee, H.H.
Molecular architecture of the G alpha i -bound TRPC5 ion channel.
Nat Commun, 14:2550-2550, 2023

PubMed Abstract: G-protein coupled receptors (GPCRs) and ion channels serve as key molecular switches through which extracellular stimuli are transformed into intracellular effects, and it has long been postulated that ion channels are direct effector molecules of the alpha subunit of G-proteins (Gα). However, no complete structural evidence supporting the direct interaction between Gα and ion channels is available. Here, we present the cryo-electron microscopy structures of the human transient receptor potential canonical 5 (TRPC5)-Gα complexes with a 4:4 stoichiometry in lipid nanodiscs. Remarkably, Gα binds to the ankyrin repeat edge of TRPC5 ~ 50 Å away from the cell membrane. Electrophysiological analysis shows that Gα increases the sensitivity of TRPC5 to phosphatidylinositol 4,5-bisphosphate (PIP), thereby rendering TRPC5 more easily opened in the cell membrane, where the concentration of PIP is physiologically regulated. Our results demonstrate that ion channels are one of the direct effector molecules of Gα proteins triggered by GPCR activation-providing a structural framework for unraveling the crosstalk between two major classes of transmembrane proteins: GPCRs and ion channels.

PubMed: 37137991
DOI: 10.1038/s41467-023-38281-3

Experimental method

ELECTRON MICROSCOPY (3.91 Å)