Structures of the calcium-activated, non-selective cation channel TRPM4

Jiangtao Guo, Ji She, Weizhong Zeng, Qingfeng Chen, Xiao Chen Bai, Youxing Jiang

Research output: Contribution to journalArticle

58 Citations (Scopus)

Abstract

TRPM4 is a calcium-activated, phosphatidylinositol-4,5-bisphosphate (PtdIns(4,5)P 2)-modulated, non-selective cation channel that belongs to the family of melastatin-related transient receptor potential (TRPM) channels. Here we present the electron cryo-microscopy structures of the mouse TRPM4 channel with and without ATP. TRPM4 consists of multiple transmembrane and cytosolic domains, which assemble into a three-tiered architecture. The N-terminal nucleotide-binding domain and the C-terminal coiled-coil participate in the tetrameric assembly of the channel; ATP binds at the nucleotide-binding domain and inhibits channel activity. TRPM4 has an exceptionally wide filter but is only permeable to monovalent cations; filter residue Gln973 is essential in defining monovalent selectivity. The S1-S4 domain and the post-S6 TRP domain form the central gating apparatus that probably houses the Ca2+-and PtdIns(4,5)P 2-binding sites. These structures provide an essential starting point for elucidating the complex gating mechanisms of TRPM4 and reveal the molecular architecture of the TRPM family.

Original languageEnglish (US)
Pages (from-to)205-209
Number of pages5
JournalNature
Volume552
Issue number7684
DOIs
StatePublished - Dec 14 2017

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Cations
Nucleotides
Adenosine Triphosphate
Calcium
Transient Receptor Potential Channels
Cryoelectron Microscopy
S 6
Monovalent Cations
Phosphatidylinositols
Binding Sites
phosphatidylinositol 5-phosphate

ASJC Scopus subject areas

  • General

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Structures of the calcium-activated, non-selective cation channel TRPM4. / Guo, Jiangtao; She, Ji; Zeng, Weizhong; Chen, Qingfeng; Bai, Xiao Chen; Jiang, Youxing.

In: Nature, Vol. 552, No. 7684, 14.12.2017, p. 205-209.

Research output: Contribution to journalArticle

Guo, Jiangtao ; She, Ji ; Zeng, Weizhong ; Chen, Qingfeng ; Bai, Xiao Chen ; Jiang, Youxing. / Structures of the calcium-activated, non-selective cation channel TRPM4. In: Nature. 2017 ; Vol. 552, No. 7684. pp. 205-209.
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