title: Orai channel pore properties and gating by STIM: implications from the Orai crystal structure.
abstract: The Orai channels are unusual, yet prominent, calcium (Ca2+) signal mediators in most cell types. Orai proteins are structurally unique, having little sequence homology with other ion channels. They are also functionally unique with exceedingly high selectivity for Ca2+, mediating both short-term Ca2+ homeostasis and long-term Ca2+ signals important for transcriptional control. Operating in the plasma membrane (PM), Orai channel regulation is unprecedented among ion channels; channel gating occurs through an elaborate intermembrane coupling with stromal interaction molecule (STIM) proteins in the endoplasmic reticulum (ER). STIM proteins function as sensors of Ca2+ stored in the ER lumen and translocate into ER-PM junctions to tether and activate Orai channels when ER Ca2+ concentration decreases. Crystallization studies reveal an unexpected hexameric structure for the Orai channel and provide important insights into the pore architecture, the structural basis of its unusual cation selectivity, and how channel gating occurs through its coupling with STIM proteins.
authors.affiliation: Department of Biochemistry, Temple University School of Medicine, 3400 North Broad Street, Philadelphia, PA 19140, USA.
authors.forename: Brad S
authors.initials: BS
authors.lastname: Rothberg
authors.forename: Youjun
authors.initials: Y
authors.lastname: Wang
authors.forename: Donald L
authors.initials: DL
authors.lastname: Gill
mesh_terms: D000818:Animals; D002118:Calcium / Q000737:chemistry / Q000378:metabolism; D015220:Calcium Channels / Q000737:chemistry* / Q000235:genetics / Q000378:metabolism; D002462:Cell Membrane / Q000378:metabolism; D018360:Crystallography, X-Ray; D029721:Drosophila Proteins / Q000737:chemistry* / Q000235:genetics / Q000378:metabolism; D004721:Endoplasmic Reticulum / Q000378:metabolism; D015640:Ion Channel Gating; D008565:Membrane Proteins / Q000737:chemistry* / Q000235:genetics / Q000378:metabolism; D008958:Models, Molecular; D009154:Mutation; D000071740:ORAI1 Protein; D011485:Protein Binding; D055503:Protein Multimerization; D017433:Protein Structure, Secondary; D017434:Protein Structure, Tertiary; D015398:Signal Transduction; D000071737:Stromal Interaction Molecule 1
chemical_list: D015220:Calcium Channels; D029721:Drosophila Proteins; D008565:Membrane Proteins; D000071740:ORAI1 Protein; C502662:Stim protein, Drosophila; D000071737:Stromal Interaction Molecule 1; C510747:olf186-F protein, Drosophila; D002118:Calcium