Medizinische Universität Graz Austria/Österreich - Forschungsportal - Medical University of Graz
Gewählte Publikation:
SHR Neuro Krebs Kardio Lipid Stoffw Microb
Muik, M; Fahrner, M; Schindl, R; Stathopulos, P; Frischauf, I; Derler, I; Plenk, P; Lackner, B; Groschner, K; Ikura, M; Romanin, C.
STIM1 couples to ORAI1 via an intramolecular transition into an extended conformation.
EMBO J. 2011; 30(9): 1678-1689.
Doi: 10.1038/emboj.2011.79
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- Führende Autor*innen der Med Uni Graz
- Schindl Rainer
- Co-Autor*innen der Med Uni Graz
- Groschner Klaus
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- Abstract:
- Stromal interaction molecule (STIM1) and ORAI1 are key components of the Ca(2+) release-activated Ca(2+) (CRAC) current having an important role in T-cell activation and mast cell degranulation. CRAC channel activation occurs via physical interaction of ORAI1 with STIM1 when endoplasmic reticulum Ca(2+) stores are depleted. Here we show, utilizing a novel STIM1-derived Förster resonance energy transfer sensor, that the ORAI1 activating small fragment (OASF) undergoes a C-terminal, intramolecular transition into an extended conformation when activating ORAI1. The C-terminal rearrangement of STIM1 does not require a functional CRAC channel, suggesting interaction with ORAI1 as sufficient for this conformational switch. Extended conformations were also engineered by mutations within the first and third coiled-coil domains in the cytosolic portion of STIM1 revealing the involvement of hydrophobic residues in the intramolecular transition. Corresponding full-length STIM1 mutants exhibited enhanced interaction with ORAI1 inducing constitutive CRAC currents, even in the absence of store depletion. We suggest that these mutant STIM1 proteins imitate a physiological activated state, which mimics the intramolecular transition that occurs in native STIM1 upon store depletion.
- Find related publications in this database (using NLM MeSH Indexing)
- Blotting, Western -
- Calcium Channels - metabolism
- Calcium Signaling - physiology
- Chromatography, Gel -
- Cloning, Molecular -
- Electrophysiology -
- Fluorescence Resonance Energy Transfer -
- Humans -
- Membrane Proteins - genetics
- Membrane Proteins - metabolism
- Microscopy, Fluorescence -
- Mutagenesis, Site-Directed -
- Neoplasm Proteins - genetics
- Neoplasm Proteins - metabolism
- ORAI1 Protein -
- Protein Conformation -
- Stromal Interaction Molecule 1 -
- Transfection -
- Find related publications in this database (Keywords)
- FRET sensor
- intramolecular transition
- ORAI1
- STIM1