Cryo-EM structures of calcium homeostasis modulator channels in diverse oligomeric assemblies.
basic_science · Level V
Where this comes from
- Record sourced from PubMed, PMID 32832629.
- Also identified by DOI 10.1126/sciadv.aba8105 and PMC identifier 7439320.
- Licence recorded as CC BY-NC.
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Abstract
Calcium homeostasis modulator (CALHM) family proteins are Ca<sup>2+</sup>-regulated adenosine triphosphate (ATP)-release channels involved in neural functions including neurotransmission in gustation. Here, we present the cryo-electron microscopy (EM) structures of killifish CALHM1, human CALHM2, and <i>Caenorhabditis elegans</i> CLHM-1 at resolutions of 2.66, 3.4, and 3.6 Å, respectively. The CALHM1 octamer structure reveals that the N-terminal helix forms the constriction site at the channel pore in the open state and modulates the ATP conductance. The CALHM2 undecamer and CLHM-1 nonamer structures show the different oligomeric stoichiometries among CALHM homologs. We further report the cryo-EM structures of the chimeric construct, revealing that the intersubunit interactions at the transmembrane domain (TMD) and the TMD-intracellular domain linker define the oligomeric stoichiometry. These findings advance our understanding of the ATP conduction and oligomerization mechanisms of CALHM channels.