STIM1 and STIM2 are endoplasmic reticulum (ER) membrane proteins that sense decreases in ER-luminal free Ca and, through a conformational change in the STIM cytoplasmic domain, control gating of the plasma membrane Ca channel ORAI1. To determine how STIM1 conveys a signal from the ER lumen to the cytoplasm, we studied the Ca-dependent conformational change of engineered STIM1 proteins in isolated ER membranes and, in parallel, physiological activation of these proteins in cells. We find that conserved "sentinel" features of the CC1 region help to prevent activation while Ca is bound to STIM ER-luminal domains. Reduced ER-luminal Ca drives a concerted conformational change, in which STIM luminal domains rearrange and the STIM transmembrane helices and initial parts of the CC1 regions pair in an extended coiled coil. This intradimer rearrangement overcomes the relatively weak CC1-SOAR/CAD interactions that hold STIM in an inactive conformation, releasing the SOAR/CAD domain to activate ORAI channels.
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http://dx.doi.org/10.1016/j.celrep.2017.12.030 | DOI Listing |
SAR QSAR Environ Res
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Research and Scientific Studies Unit, College of Nursing and Health Sciences, Jazan University, Jazan, Saudi Arabia.
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January 2025
Department of Biochemistry and Molecular Biophysics, Washington University in St. Louis, School of Medicine, St. Louis, MO, USA.
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January 2025
Department of Chemistry, Waterloo Institute for Nanotechnology, University of Waterloo, Waterloo, Ontario N2L 3G1, Canada.
Rare earth elements (REEs) are widely used in various high-tech industries. Developing affinity ligands that can detect and distinguish REEs is at the forefront of analytical chemistry. It is also interesting to understand the limits of natural biomolecules for the recognition of REEs.
View Article and Find Full Text PDFInt J Biol Macromol
December 2024
Department of Applied Sciences, Northumbria University, Newcastle Upon Tyne NE1 8ST, Tyne & Wear, England, United Kingdom. Electronic address:
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State Key Laboratory of Green Pesticide, International Joint Research Center for Intelligent Biosensor Technology and Health, Central China Normal University, Wuhan 430079, PR China. Electronic address:
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