title: Molecular biophysics of Orai store-operated Ca2+ channels.
abstract: Upon endoplasmic reticulum Ca(2+) store depletion, Orai channels in the plasma membrane are activated directly by endoplasmic reticulum-resident STIM proteins to generate the Ca(2+)-selective, Ca(2+) release-activated Ca(2+) (CRAC) current. After the molecular identification of Orai, a plethora of functional and biochemical studies sought to compare Orai homologs, determine their stoichiometry, identify structural domains responsible for the biophysical fingerprint of the CRAC current, identify the physiological functions, and investigate Orai homologs as potential therapeutic targets. Subsequently, the solved crystal structure of Drosophila Orai (dOrai) substantiated many findings from structure-function studies, but also revealed an unexpected hexameric structure. In this review, we explore Orai channels as elucidated by functional and biochemical studies, analyze the dOrai crystal structure and its implications for Orai channel function, and present newly available information from molecular dynamics simulations that shed light on Orai channel gating and permeation.
authors.affiliation: Department of Physiology and Biophysics, University of California at Irvine, Irvine, California.
authors.forename: Anna
authors.initials: A
authors.lastname: Amcheslavsky
authors.affiliation: Department of Chemistry, University of California at Irvine, Irvine, California.
authors.forename: Mona L
authors.initials: ML
authors.lastname: Wood
authors.affiliation: Department of Physiology and Biophysics, University of California at Irvine, Irvine, California.
authors.forename: Andriy V
authors.initials: AV
authors.lastname: Yeromin
authors.affiliation: Department of Physiology and Biophysics, University of California at Irvine, Irvine, California; Department of Neurobiology and Behavior, University of California at Irvine, Irvine, California.
authors.forename: Ian
authors.initials: I
authors.lastname: Parker
authors.affiliation: Department of Chemistry, University of California at Irvine, Irvine, California.
authors.forename: J Alfredo
authors.initials: JA
authors.lastname: Freites
authors.affiliation: Department of Chemistry, University of California at Irvine, Irvine, California.
authors.forename: Douglas J
authors.initials: DJ
authors.lastname: Tobias
authors.affiliation: Department of Physiology and Biophysics, University of California at Irvine, Irvine, California; Institute for Immunology, University of California at Irvine, Irvine, California. Electronic address: mcahalan@uci.edu.
authors.forename: Michael D
authors.initials: MD
authors.lastname: Cahalan
mesh_terms: D000595:Amino Acid Sequence; D000818:Animals; D015220:Calcium Channels / Q000737:chemistry* / Q000235:genetics / Q000378:metabolism; D020013:Calcium Signaling; D006801:Humans; D015640:Ion Channel Gating; D008969:Molecular Sequence Data
chemical_list: D015220:Calcium Channels