title: Mechanistic view on domains mediating STIM1-Orai coupling.
abstract: Calcium (Ca2+) entry into non-excitable cells is mainly carried by store-operated channels, which serve essential functions ranging from regulation of transcription to cell growth. The best-characterized store-operated current, initially discovered in T lymphocytes and mast cells, is the Ca2+ release-activated Ca2+ (CRAC) current. The search for the molecular components of the CRAC channel has recently identified stromal interaction molecule 1 (STIM1) as the Ca2+ sensor in the endoplasmic reticulum (ER) and Orai1 as the CRAC channel pore. ER store depletion results in formation of STIM1 puncta that trigger Ca2+ influx via Orai1 channels. This review covers the role of domains within STIM1 and Orai and enlightens their function in the STIM1/Orai coupling process. Moreover, a molecular interpretation focuses on interactions between cytosolic portions of STIM1 and Orai together with a mechanistic view on the loss of function of the SCID (severe combined immunodeficiency)-linked Orai1 R91W mutant channel. The architecture of the selectivity filter of Orai channels is finally elucidated based on permeation properties of Orai pore mutants.
authors.affiliation: Institute of Biophysics, University of Linz, Linz, Austria.
authors.forename: Marc
authors.initials: M
authors.lastname: Fahrner
authors.forename: Martin
authors.initials: M
authors.lastname: Muik
authors.forename: Isabella
authors.initials: I
authors.lastname: Derler
authors.forename: Rainer
authors.initials: R
authors.lastname: Schindl
authors.forename: Reinhard
authors.initials: R
authors.lastname: Fritsch
authors.forename: Irene
authors.initials: I
authors.lastname: Frischauf
authors.forename: Christoph
authors.initials: C
authors.lastname: Romanin
mesh_terms: D000818:Animals; D002118:Calcium / Q000378:metabolism*; D015220:Calcium Channels / Q000737:chemistry / Q000235:genetics / Q000378:metabolism*; D003600:Cytosol / Q000378:metabolism; D006801:Humans; D008565:Membrane Proteins / Q000737:chemistry / Q000235:genetics / Q000378:metabolism*; D011485:Protein Binding
chemical_list: D015220:Calcium Channels; D008565:Membrane Proteins; D002118:Calcium