title: Structural aspects of calcium-release activated calcium channel function.
abstract: Store-operated calcium (Ca(2+)) entry is the process by which molecules located on the endo/sarcoplasmic reticulum (ER/SR) respond to decreased luminal Ca(2+) levels by signaling Ca(2+) release activated Ca(2+) channels (CRAC) channels to open on the plasma membrane (PM). This activation of PM CRAC channels provides a sustained cytosolic Ca(2+) elevation associated with myriad physiological processes. The identities of the molecules which mediate SOCE include stromal interaction molecules (STIMs), functioning as the ER/SR luminal Ca(2+) sensors, and Orai proteins, forming the PM CRAC channels. This review examines the current available high-resolution structural information on these CRAC molecular components with particular focus on the solution structures of the luminal STIM Ca(2+) sensing domains, the crystal structures of cytosolic STIM fragments, a closed Orai hexameric crystal structure and a structure of an Orai1 N-terminal fragment in complex with calmodulin. The accessible structural data are discussed in terms of potential mechanisms of action and cohesiveness with functional observations.
authors.affiliation: Princess Margaret Cancer Centre; Department of Medical Biophysics; University of Toronto; Toronto, ON, Canada.
authors.forename: Peter B
authors.initials: PB
authors.lastname: Stathopulos
authors.affiliation: Princess Margaret Cancer Centre; Department of Medical Biophysics; University of Toronto; Toronto, ON, Canada.
authors.forename: Mitsuhiko
authors.initials: M
authors.lastname: Ikura
mesh_terms: D000818:Animals; D015220:Calcium Channels / Q000737:chemistry* / Q000378:metabolism; D015815:Cell Adhesion Molecules / Q000737:chemistry* / Q000378:metabolism; D029721:Drosophila Proteins / Q000737:chemistry* / Q000378:metabolism; D006801:Humans; D008565:Membrane Proteins / Q000737:chemistry* / Q000378:metabolism; D009363:Neoplasm Proteins / Q000737:chemistry* / Q000378:metabolism; D000071740:ORAI1 Protein; D011487:Protein Conformation; D000071737:Stromal Interaction Molecule 1; D000071738:Stromal Interaction Molecule 2
chemical_list: D015220:Calcium Channels; D015815:Cell Adhesion Molecules; D029721:Drosophila Proteins; D008565:Membrane Proteins; D009363:Neoplasm Proteins; D000071740:ORAI1 Protein; C103530:STIM1 protein, human; C513279:STIM2 protein, human; D000071737:Stromal Interaction Molecule 1; D000071738:Stromal Interaction Molecule 2; C510747:olf186-F protein, Drosophila
keywords: Orai channel proteins; calcium release activated calcium; calmodulin; store operated calcium entry; stromal interaction molecules