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TitleStructure and assembly of calcium homeostasis modulator proteins.
Journal, issue, pagesNat Struct Mol Biol, Vol. 27, Issue 2, Page 150-159, Year 2020
Publish dateJan 27, 2020
AuthorsJohanna L Syrjanen / Kevin Michalski / Tsung-Han Chou / Timothy Grant / Shanlin Rao / Noriko Simorowski / Stephen J Tucker / Nikolaus Grigorieff / Hiro Furukawa /
PubMed AbstractThe biological membranes of many cell types contain large-pore channels through which a wide variety of ions and metabolites permeate. Examples include connexin, innexin and pannexin, which form gap ...The biological membranes of many cell types contain large-pore channels through which a wide variety of ions and metabolites permeate. Examples include connexin, innexin and pannexin, which form gap junctions and/or bona fide cell surface channels. The most recently identified large-pore channels are the calcium homeostasis modulators (CALHMs), through which ions and ATP permeate in a voltage-dependent manner to control neuronal excitability, taste signaling and pathologies of depression and Alzheimer's disease. Despite such critical biological roles, the structures and patterns of their oligomeric assembly remain unclear. Here, we reveal the structures of two CALHMs, chicken CALHM1 and human CALHM2, by single-particle cryo-electron microscopy (cryo-EM), which show novel assembly of the four transmembrane helices into channels of octamers and undecamers, respectively. Furthermore, molecular dynamics simulations suggest that lipids can favorably assemble into a bilayer within the larger CALHM2 pore, but not within CALHM1, demonstrating the potential correlation between pore size, lipid accommodation and channel activity.
External linksNat Struct Mol Biol / PubMed:31988524 / PubMed Central
MethodsEM (single particle)
Resolution3.48 - 3.87 Å
Structure data

EMDB-21140, PDB-6vai:
Cryo-EM structure of a dimer of undecameric human CALHM2
Method: EM (single particle) / Resolution: 3.68 Å

EMDB-21141, PDB-6vak:
Cryo-EM structure of human CALHM2
Method: EM (single particle) / Resolution: 3.48 Å

EMDB-21142, PDB-6val:
Cryo-EM structure of an undecameric chicken CALHM1 and human CALHM2 chimera
Method: EM (single particle) / Resolution: 3.87 Å

EMDB-21143, PDB-6vam:
Cryo-EM structure of octameric chicken CALHM1
Method: EM (single particle) / Resolution: 3.63 Å

Source
  • homo sapiens (human)
  • gallus gallus (chicken)
  • aequorea victoria (jellyfish)
KeywordsMEMBRANE PROTEIN / taste / assembly / calcium / gap junction / chimera

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