PUBLICATION
Cryo-EM structure of the heptameric calcium homeostasis modulator 1 channel
- Authors
- Ren, Y., Li, Y., Wang, Y., Wen, T., Lu, X., Chang, S., Zhang, X., Shen, Y., Yang, X.
- ID
- ZDB-PUB-220329-2
- Date
- 2022
- Source
- The Journal of biological chemistry 298(5): 101838 (Journal)
- Registered Authors
- Keywords
- ATP permeation, CALHM1, Calcium homeostasis modulator, assembly, cryo-EM, gating mechanism
- MeSH Terms
-
- Adenosine Triphosphate*/metabolism
- Animals
- Calcium/metabolism
- Calcium Channels*/chemistry
- Cryoelectron Microscopy
- Homeostasis
- Zebrafish
- Zebrafish Proteins*/chemistry
- PubMed
- 35339491 Full text @ J. Biol. Chem.
Citation
Ren, Y., Li, Y., Wang, Y., Wen, T., Lu, X., Chang, S., Zhang, X., Shen, Y., Yang, X. (2022) Cryo-EM structure of the heptameric calcium homeostasis modulator 1 channel. The Journal of biological chemistry. 298(5):101838.
Abstract
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 Danio 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.
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