title: Structural and functional similarities of calcium homeostasis modulator 1 (CALHM1) ion channel with connexins, pannexins, and innexins.
abstract: CALHM1 (calcium homeostasis modulator 1) forms a plasma membrane ion channel that mediates neuronal excitability in response to changes in extracellular Ca(2+) concentration. Six human CALHM homologs exist with no homology to other proteins, although CALHM1 is conserved across >20 species. Here we demonstrate that CALHM1 shares functional and quaternary and secondary structural similarities with connexins and evolutionarily distinct innexins and their vertebrate pannexin homologs. A CALHM1 channel is a hexamer, comprised of six monomers, each of which possesses four transmembrane domains, cytoplasmic amino and carboxyl termini, an amino-terminal helix, and conserved extracellular cysteines. The estimated pore diameter of the CALHM1 channel is ∼14 Å, enabling permeation of large charged molecules. Thus, CALHMs, connexins, and pannexins and innexins are structurally related protein families with shared and distinct functional properties.
authors.affiliation: Department of Physiology, Perelman School of Medicine, University of Pennsylvania, Philadelphia, Pennsylvania 19104-6085, USA.
authors.forename: Adam P
authors.initials: AP
authors.lastname: Siebert
authors.forename: Zhongming
authors.initials: Z
authors.lastname: Ma
authors.forename: Jeremy D
authors.initials: JD
authors.lastname: Grevet
authors.forename: Angelo
authors.initials: A
authors.lastname: Demuro
authors.forename: Ian
authors.initials: I
authors.lastname: Parker
authors.forename: J Kevin
authors.initials: JK
authors.lastname: Foskett
mesh_terms: D000818:Animals; D015220:Calcium Channels / Q000737:chemistry* / Q000235:genetics / Q000378:metabolism*; D045744:Cell Line, Tumor; D017630:Connexins / Q000737:chemistry* / Q000235:genetics / Q000378:metabolism*; D006801:Humans; D008562:Membrane Glycoproteins / Q000737:chemistry* / Q000235:genetics / Q000378:metabolism*; D051379:Mice; D017433:Protein Structure, Secondary; D017434:Protein Structure, Tertiary; D040681:Structural Homology, Protein
chemical_list: C530077:CALHM1 protein, human; C575356:CALHM1 protein, mouse; D015220:Calcium Channels; D017630:Connexins; D008562:Membrane Glycoproteins