7DSE

CALHM1 close state with ordered CTH

Summary for 7DSE

• Entry DOI: 10.2210/pdb7dse/pdb
• EMDB information: 30832
• Descriptor: Calcium homeostasis modulator 1, 2-acetamido-2-deoxy-beta-D-glucopyranose (2 entities in total)
• Functional Keywords: close state, membrane protein
• Biological source: Danio rerio (zebrafish)
• Total number of polymer chains: 7
• Total formula weight: 290043.97

Authors

Ren, Y.,Yang, X.,Shen, Y.Q. (deposition date: 2020-12-30, release date: 2022-01-05, Last modification date: 2024-11-13)

Primary citation

Ren, Y.,Li, Y.,Wang, Y.,Wen, T.,Lu, X.,Chang, S.,Zhang, X.,Shen, Y.,Yang, X.
Cryo-EM structure of the heptameric calcium homeostasis modulator 1 channel.
J.Biol.Chem., 298:101838-101838, 2022

PubMed Abstract: 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.

PubMed: 35339491
DOI: 10.1016/j.jbc.2022.101838

Experimental method

ELECTRON MICROSCOPY (3.2 Å)