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Structure paper

TitleStructures of the calcium-activated, non-selective cation channel TRPM4.
Journal, issue, pagesNature, Vol. 552, Issue 7684, Page 205-209, Year 2017
Publish dateDec 14, 2017
AuthorsJiangtao Guo / Ji She / Weizhong Zeng / Qingfeng Chen / Xiao-Chen Bai / Youxing Jiang /
PubMed AbstractTRPM4 is a calcium-activated, phosphatidylinositol-4,5-bisphosphate (PtdIns(4,5)P) -modulated, non-selective cation channel that belongs to the family of melastatin-related transient receptor ...TRPM4 is a calcium-activated, phosphatidylinositol-4,5-bisphosphate (PtdIns(4,5)P) -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 Ca- and PtdIns(4,5)P-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.
External linksNature / PubMed:29211714 / PubMed Central
MethodsEM (single particle)
Resolution2.88 - 3.54 Å
Structure data

7081

6bcj

EMDB-7081, PDB-6bcj:
cryo-EM structure of TRPM4 in apo state with short coiled coil at 3.1 angstrom resolution
Method: EM (single particle) / Resolution: 3.14 Å

7082

6bcl

EMDB-7082, PDB-6bcl:
cryo-EM structure of TRPM4 in apo state with long coiled coil at 3.5 angstrom resolution
Method: EM (single particle) / Resolution: 3.54 Å

7083

6bco

EMDB-7083, PDB-6bco:
cryo-EM structure of TRPM4 in ATP bound state with short coiled coil at 2.9 angstrom resolution
Method: EM (single particle) / Resolution: 2.88 Å

7085

6bcq

EMDB-7085, PDB-6bcq:
cryo-EM structure of TRPM4 in ATP bound state with long coiled coil at 3.3 angstrom resolution
Method: EM (single particle) / Resolution: 3.25 Å

Chemicals

ChemComp-NA:
Unknown entry

ChemComp-HOH:
WATER

ChemComp-ATP:
ADENOSINE-5'-TRIPHOSPHATE / ATP, energy-carrying molecule*YM

Source
  • mus musculus (house mouse)
KeywordsTRANSPORT PROTEIN / ion channel

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