Department of Physiology, Perelman School of Medicine, University of Pennsylvania, Philadelphia, Pennsylvania 19104-6085, USA.
J Biol Chem. 2013 Mar 1;288(9):6140-53. doi: 10.1074/jbc.M112.409789. Epub 2013 Jan 8.
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.
CALHM1（钙稳态调节剂 1）形成质膜离子通道，响应细胞外 Ca（2+）浓度的变化调节神经元兴奋性。存在 6 个人类 CALHM 同源物，与其他蛋白质没有同源性，尽管 CALHM1 在超过 20 个物种中是保守的。在这里，我们证明 CALHM1 与连接蛋白和进化上不同的间隙连接蛋白及其脊椎动物的 pannexin 同源物具有功能和四级、二级结构相似性。CALHM1 通道是由六个单体组成的六聚体，每个单体具有四个跨膜结构域、细胞质氨基和羧基末端、氨基末端螺旋和保守的细胞外半胱氨酸。CALHM1 通道的估计孔径约为 14 Å，允许大的带电荷分子通过。因此，CALHMs、连接蛋白和 pannexin 以及间隙连接蛋白是结构相关的蛋白质家族，具有共同和独特的功能特性。
