8SLP

Cryo-EM structure of the rat TRPM5 channel in 2mM calcium, high-2

Summary for 8SLP

• Entry DOI: 10.2210/pdb8slp/pdb
• EMDB information: 40574 40575 40576 40577 40578 40579 40580 40581 40595
• Descriptor: Transient receptor potential cation channel subfamily M member 5, CALCIUM ION (2 entities in total)
• Functional Keywords: ion channel, transient receptor potential, trp, transient receptor potential melastatin 5, trpm5, membrane protein, transport protein
• Biological source: Rattus norvegicus (Norway rat)
• Total number of polymer chains: 4
• Total formula weight: 529727.50

Authors

Karuppan, S.,Schrag, L.G.,Jara-Oseguera, A.,Zubcevic, L. (deposition date: 2023-04-24, release date: 2024-07-03, Last modification date: 2024-07-10)

Primary citation

Karuppan, S.,Schrag, L.G.,Pastrano, C.M.,Jara-Oseguera, A.,Zubcevic, L.
Structural dynamics at cytosolic interprotomer interfaces control gating of a mammalian TRPM5 channel.
Proc.Natl.Acad.Sci.USA, 121:e2403333121-e2403333121, 2024

PubMed Abstract: The transient receptor potential melastatin (TRPM) tetrameric cation channels are involved in a wide range of biological functions, from temperature sensing and taste transduction to regulation of cardiac function, inflammatory pain, and insulin secretion. The structurally conserved TRPM cytoplasmic domains make up >70 % of the total protein. To investigate the mechanism by which the TRPM cytoplasmic domains contribute to gating, we employed electrophysiology and cryo-EM to study TRPM5-a channel that primarily relies on activation via intracellular Ca. Here, we show that activation of mammalian TRPM5 channels is strongly altered by Ca-dependent desensitization. Structures of rat TRPM5 identify a series of conformational transitions triggered by Ca binding, whereby formation and dissolution of cytoplasmic interprotomer interfaces appear to control activation and desensitization of the channel. This study shows the importance of the cytoplasmic assembly in TRPM5 channel function and sets the stage for future investigations of other members of the TRPM family.

PubMed: 38923985
DOI: 10.1073/pnas.2403333121

Experimental method

ELECTRON MICROSCOPY (3.8 Å)