Structural dynamics at cytosolic interprotomer interfaces control gating of a mammalian TRPM5 channel.

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 Ca²⁺. Here, we show that activation of mammalian TRPM5 channels is strongly altered by Ca²⁺-dependent desensitization. Structures of rat TRPM5 identify a series of conformational transitions triggered by Ca²⁺ bin

SUBMITTER: Karuppan S 

PROVIDER: S-EPMC11228501 | biostudies-literature | 2024 Jul

REPOSITORIES: biostudies-literature