title: Cooperative Binding of Stromal Interaction Molecule 1 (STIM1) to the N and C Termini of Calcium Release-activated Calcium Modulator 1 (Orai1).
abstract: Calcium flux through store-operated calcium entry is a central regulator of intracellular calcium signaling. The two key components of the store-operated calcium release-activated calcium channel are the Ca(2+)-sensing protein stromal interaction molecule 1 (STIM1) and the channel pore-forming protein Orai1. During store-operated calcium entry activation, calcium depletion from the endoplasmic reticulum triggers a series of conformational changes in STIM1 that unmask a minimal Orai1-activating domain (CRAC activation region (CAD)). To gate Orai1 channels, the exposed STIM1-activating domain binds to two sites in Orai1, one in the N terminus and one in the C terminus. Whether the two sites operate as distinct binding domains or cooperate in CAD binding is unknown. In this study, we show that the N and C-terminal domains of Orai1 synergistically contribute to the interaction with STIM1 and couple STIM1 binding with channel gating and modulation of ion selectivity.
authors.affiliation: From the Department of Molecular and Cell Biology and.
authors.forename: Raz
authors.initials: R
authors.lastname: Palty
authors.affiliation: From the Department of Molecular and Cell Biology and Helen Wills Neuroscience Institute, University of California Berkeley, Berkeley, California 94720 and the Physical Bioscience Division, Lawrence Berkeley National Laboratory, Berkeley, California 94720 ehud@berkeley.edu.
authors.forename: Ehud Y
authors.initials: EY
authors.lastname: Isacoff
mesh_terms: D015220:Calcium Channels / Q000737:chemistry* / Q000378:metabolism*; D057809:HEK293 Cells; D006801:Humans; D015640:Ion Channel Gating; D007477:Ions; D008565:Membrane Proteins / Q000378:metabolism*; D050505:Mutant Proteins / Q000378:metabolism; D009363:Neoplasm Proteins / Q000378:metabolism*; D000071740:ORAI1 Protein; D011485:Protein Binding; D017434:Protein Structure, Tertiary; D000071737:Stromal Interaction Molecule 1
chemical_list: D015220:Calcium Channels; D007477:Ions; D008565:Membrane Proteins; D050505:Mutant Proteins; D009363:Neoplasm Proteins; D000071740:ORAI1 Protein; C510746:ORAI1 protein, human; C103530:STIM1 protein, human; D000071737:Stromal Interaction Molecule 1
keywords: calcium channel; calcium release-activated calcium channel protein 1 (ORAI1); gating; ion channel; stromal interaction molecule 1 (STIM1)