Medizinische Universität Graz - Research portal
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SHR Neuro Cancer Cardio Lipid Metab Microb
Stathopulos, PB; Schindl, R; Fahrner, M; Zheng, L; Gasmi-Seabrook, GM; Muik, M; Romanin, C; Ikura, M.
STIM1/Orai1 coiled-coil interplay in the regulation of store-operated calcium entry.
Nat Commun. 2013; 4(48): 2963-2963.
Doi: 10.1038/ncomms3963
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- Co-authors Med Uni Graz
- Schindl Rainer
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- Abstract:
- Orai1 calcium channels in the plasma membrane are activated by stromal interaction molecule-1 (STIM1), an endoplasmic reticulum calcium sensor, to mediate store-operated calcium entry (SOCE). The cytosolic region of STIM1 contains a long putative coiled-coil (CC)1 segment and shorter CC2 and CC3 domains. Here we present solution nuclear magnetic resonance structures of a trypsin-resistant CC1-CC2 fragment in the apo and Orai1-bound states. Each CC1-CC2 subunit forms a U-shaped structure that homodimerizes through antiparallel interactions between equivalent α-helices. The CC2:CC2' helix pair clamps two identical acidic Orai1 C-terminal helices at opposite ends of a hydrophobic/basic STIM-Orai association pocket. STIM1 mutants disrupting CC1:CC1' interactions attenuate, while variants promoting CC1 stability spontaneously activate Orai1 currents. CC2 mutations cause remarkable variability in Orai1 activation because of a dual function in binding Orai1 and autoinhibiting STIM1 oligomerization via interactions with CC3. We conclude that SOCE is activated through dynamic interplay between STIM1 and Orai1 helices.
- Find related publications in this database (using NLM MeSH Indexing)
- Amino Acid Sequence -
- Calcium - metabolism
- Calcium Channels - metabolism
- Cytosol - metabolism
- Dimerization -
- Endoplasmic Reticulum - metabolism
- HEK293 Cells -
- Humans -
- Magnetic Resonance Spectroscopy -
- Membrane Proteins - metabolism
- Molecular Conformation -
- Molecular Sequence Data -
- Mutagenesis -
- Mutation -
- Neoplasm Proteins - metabolism
- ORAI1 Protein -
- Patch-Clamp Techniques -
- Stromal Interaction Molecule 1 -