Medizinische Universität Graz Austria/Österreich - Forschungsportal - Medical University of Graz
Gewählte Publikation:
SHR Neuro Krebs Kardio Lipid Stoffw Microb
Zheng, L; Stathopulos, PB; Schindl, R; Li, GY; Romanin, C; Ikura, M.
Auto-inhibitory role of the EF-SAM domain of STIM proteins in store-operated calcium entry.
Proc Natl Acad Sci U S A. 2011; 108(4): 1337-1342.
Doi: 10.1073/pnas.1015125108
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- Co-Autor*innen der Med Uni Graz
- Schindl Rainer
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- Abstract:
- Stromal interaction molecules (STIM)s function as endoplasmic reticulum calcium (Ca(2+)) sensors that differentially regulate plasma membrane Ca(2+) release activated Ca(2+) channels in various cells. To probe the structural basis for the functional differences between STIM1 and STIM2 we engineered a series of EF-hand and sterile α motif (SAM) domain (EF-SAM) chimeras, demonstrating that the STIM1 Ca(2+)-binding EF-hand and the STIM2 SAM domain are major contributors to the autoinhibition of oligomerization in each respective isoform. Our nuclear magnetic resonance (NMR) derived STIM2 EF-SAM structure provides a rationale for an augmented stability, which involves a 54° pivot in the EF-hand:SAM domain orientation permissible by an expanded nonpolar cleft, ionic interactions, and an enhanced hydrophobic SAM core, unique to STIM2. Live cells expressing "super-unstable" or "super-stable" STIM1/STIM2 EF-SAM chimeras in the full-length context show a remarkable correlation with the in vitro data. Together, our data suggest that divergent Ca(2+)- and SAM-dependent stabilization of the EF-SAM fold contributes to the disparate regulation of store-operated Ca(2+) entry by STIM1 and STIM2.
- Find related publications in this database (using NLM MeSH Indexing)
- Amino Acid Sequence -
- Binding Sites -
- Calcium - metabolism
- Calcium Channels - metabolism
- Cell Adhesion Molecules - chemistry
- Cell Adhesion Molecules - genetics
- Cell Adhesion Molecules - metabolism
- EF Hand Motifs -
- Endoplasmic Reticulum - metabolism
- HEK293 Cells -
- HeLa Cells -
- Humans -
- Hydrophobic and Hydrophilic Interactions -
- Luminescent Proteins - genetics
- Luminescent Proteins - metabolism
- Magnetic Resonance Spectroscopy -
- Membrane Potentials -
- Membrane Proteins - chemistry
- Membrane Proteins - genetics
- Membrane Proteins - metabolism
- Microscopy, Fluorescence -
- Models, Molecular -
- Molecular Sequence Data -
- Neoplasm Proteins - chemistry
- Neoplasm Proteins - genetics
- Neoplasm Proteins - metabolism
- ORAI1 Protein -
- Protein Binding -
- Protein Structure, Secondary -
- Protein Structure, Tertiary -
- Sequence Homology, Amino Acid -
- Stromal Interaction Molecule 1 -
- Stromal Interaction Molecule 2 -
- Transfection -
- Find related publications in this database (Keywords)
- NMR structure
- protein stability
- STIM2
- store-operated calcium entry