PUBLICATION
Cryo-EM structure of the calcium homeostasis modulator 1 channel
- Authors
- Ren, Y., Wen, T., Xi, Z., Li, S., Lu, J., Zhang, X., Yang, X., Shen, Y.
- ID
- ZDB-PUB-200825-8
- Date
- 2020
- Source
- Science advances 6: eaba8161 (Journal)
- Registered Authors
- Keywords
- none
- MeSH Terms
-
- Calcium*/metabolism
- Calcium Channels*/chemistry
- Cryoelectron Microscopy
- Gap Junctions/metabolism
- Homeostasis
- PubMed
- 32832630 Full text @ Sci Adv
Citation
Ren, Y., Wen, T., Xi, Z., Li, S., Lu, J., Zhang, X., Yang, X., Shen, Y. (2020) Cryo-EM structure of the calcium homeostasis modulator 1 channel. Science advances. 6:eaba8161.
Abstract
Calcium homeostasis modulator 1 (CALHM1) is a voltage-gated ATP release channel that plays an important role in neural gustatory signaling and the pathogenesis of Alzheimer's disease. Here, we present a cryo-electron microscopy structure of full-length Ca2+-free CALHM1 from Danio rerio at an overall resolution of 3.1 Å. Our structure reveals an octameric architecture with a wide pore diameter of ~20 Å, presumably representing the active conformation. The overall structure is substantially different from that of the isoform CALHM2, which forms both undecameric hemichannels and gap junctions. The N-terminal small helix folds back to the pore and forms an antiparallel interaction with transmembrane helix 1. Structural analysis revealed that the extracellular loop 1 region within the dimer interface may contribute to oligomeric assembly. A positive potential belt inside the pore was identified that may modulate ion permeation. Our structure offers insights into the assembly and gating mechanism of the CALHM1 channel.
Genes / Markers
Expression
Phenotype
Mutations / Transgenics
Human Disease / Model
Sequence Targeting Reagents
Fish
Orthology
Engineered Foreign Genes
Mapping