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Structure paper

TitleCryo-EM structure of the heptameric calcium homeostasis modulator 1 channel.
Journal, issue, pagesJ Biol Chem, Vol. 298, Issue 5, Page 101838, Year 2022
Publish dateMar 24, 2022
AuthorsYue Ren / Yang Li / Yaojie Wang / Tianlei Wen / Xuhang Lu / Shenghai Chang / Xing Zhang / Yuequan Shen / Xue Yang /
PubMed AbstractCalcium homeostasis modulator 1 (CALHM1) is a voltage- and Ca-gated ATP channel that plays an important role in neuronal signaling. However, as the previously reported CALHM structures are all in the ...Calcium homeostasis modulator 1 (CALHM1) is a voltage- and Ca-gated ATP channel that plays an important role in neuronal signaling. However, as the previously reported CALHM structures are all in the ATP-conducting state, the gating mechanism of ATP permeation is still elusive. Here, we report cryo-EM reconstructions of two Danio rerio CALHM1 heptamers with ordered or flexible long C-terminal helices at resolutions of 3.2 Å and 2.9 Å, respectively, and one D. rerio CALHM1 octamer with flexible long C-terminal helices at a resolution of 3.5 Å. Structural analysis shows that the heptameric CALHM1s are in an ATP-nonconducting state with a central pore diameter of approximately 6.6 Å. Compared with those inside the octameric CALHM1, the N-helix inside the heptameric CALHM1 is in the "down" position to avoid steric clashing with the adjacent TM1 helix. Molecular dynamics simulations show that as the N-helix moves from the "down" position to the "up" position, the pore size of ATP molecule permeation increases significantly. Our results provide important information for elucidating the mechanism of ATP molecule permeation in the CALHM1 channel.
External linksJ Biol Chem / PubMed:35339491 / PubMed Central
MethodsEM (single particle)
Resolution2.9 - 3.5 Å
Structure data

30830

7dsc

EMDB-30830, PDB-7dsc:
CALHM1 open state with disordered CTH
Method: EM (single particle) / Resolution: 3.5 Å

30831

7dsd

EMDB-30831, PDB-7dsd:
CALHM1 close state with disordered CTH
Method: EM (single particle) / Resolution: 2.9 Å

30832

7dse

EMDB-30832, PDB-7dse:
CALHM1 close state with ordered CTH
Method: EM (single particle) / Resolution: 3.2 Å

Chemicals

ChemComp-NAG:
2-acetamido-2-deoxy-beta-D-glucopyranose / N-Acetylglucosamine

Source
  • danio rerio (zebrafish)
KeywordsMEMBRANE PROTEIN / channel / close state

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