6lmv
Cryo-EM structure of the C. elegans CLHM-1Cryo-EM structure of the C. elegans CLHM-1
Structural highlights
Function[CLHM1_CAEEL] Pore-forming subunit of a voltage-gated ion channel. Permeable to monovalent cations, divalent cations and anions with selectivity Ca(2+) > Mg(2+) > Na(+) = K(+) > Cl(-). Acts both as a voltage-gated and calcium-activated ion channel. Required for normal locomotion.[1] Publication Abstract from PubMedCalcium homeostasis modulator (CALHM) family proteins are Ca(2+)-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 Caenorhabditis elegans CLHM-1 at resolutions of 2.66, 3.4, and 3.6 A, 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. Cryo-EM structures of calcium homeostasis modulator channels in diverse oligomeric assemblies.,Demura K, Kusakizako T, Shihoya W, Hiraizumi M, Nomura K, Shimada H, Yamashita K, Nishizawa T, Taruno A, Nureki O Sci Adv. 2020 Jul 17;6(29):eaba8105. doi: 10.1126/sciadv.aba8105. eCollection, 2020 Jul. PMID:32832629[2] From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine. References
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