Cooperative Binding of Stromal Interaction Molecule 1 (STIM1) to the N and C Termini of Calcium Release-activated Calcium Modulator 1 (Orai1) |
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| Authors: | Raz Palty Ehud Y. Isacoff |
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| 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 |
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| 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 Ca2+-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. |
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| Keywords: | calcium channel calcium release-activated calcium channel protein 1 (ORAI1) gating ion channel stromal interaction molecule 1 (STIM1) |
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