biostudies-literatureUnknown298(5)Ren YCalcium homeostasis modulator 1 (CALHM1) is a voltage- and Ca²⁺-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 tThe Journal of biological chemistry101838https://www.ebi.ac.uk/biostudies/studies/S-EPMC9035704biostudies-literatureCryo-EM structure of the heptameric calcium homeostasis modulator 1 channel.PMC9035704Yang XLi YLu XRen YZhang XChang SWang YShen YWen TfalseCryo-EM structure of the heptameric calcium homeostasis modulator 1 channel.Calcium homeostasis modulator 1 (CALHM1) is a voltage- and Ca²⁺-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 t2022-01-01T00:00:00Z2022 May2026-05-31T06:06:25.194Z2025-02-19T01:55:34.471ZS-EPMC90357043533949110.1016/j.jbc.2022.101838