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Structural features of STIM and Orai underlying store-operated calcium entry.

07:00 EST 1st February 2019 | BioPortfolio

Summary of "Structural features of STIM and Orai underlying store-operated calcium entry."

Store-operated calcium entry (SOCE) through Orai channels is triggered by receptor-stimulated depletion of Ca from the ER. Orai1 is unique in terms of its activation mechanism, biophysical properties, and structure, and its precise regulation is essential for human health. Recent studies have begun to reveal the structural basis of the major steps in the SOCE pathway and how the system is reliably suppressed in resting cells but able to respond robustly to ER Ca depletion. In this review, we discuss current models describing the activation of ER Ca sensor STIM1, its binding to Orai1, propagation of the binding signal from the channel periphery to the central pore, and the resulting conformational changes underlying opening of the highly Ca selective Orai1 channel.

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This article was published in the following journal.

Name: Current opinion in cell biology
ISSN: 1879-0410
Pages: 90-98

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Medical and Biotech [MESH] Definitions

Signal transduction mechanisms whereby calcium mobilization (from outside the cell or from intracellular storage pools) to the cytoplasm is triggered by external stimuli. Calcium signals are often seen to propagate as waves, oscillations, spikes, sparks, or puffs. The calcium acts as an intracellular messenger by activating calcium-responsive proteins.

Intracellular signaling peptides and proteins that bind to CALCIUM. They undergo allosteric changes when bound to CALCIUM that affects their interaction with other signal-transducing molecules. They differ from CALCIUM-SENSING RECEPTORS which sense extracellular calcium levels.

Protein modules that function in the targeting of proteins to CELL MEMBRANES. They consist of an eight-stranded anti-parallel beta-sandwich composed of a pair of four-stranded beta-sheets. This structural unit forms a pocket on the membrane-interacting face of the protein and co-ordinates the binding of 2 to 3 calcium ions; however, not all C2 domains bind calcium. Examples of C2 domain-containing proteins include PROTEIN KINASE C and PTEN PHOSPHOHYDROLASE.

A class of G-protein-coupled receptors that react to varying extracellular CALCIUM levels. Calcium-sensing receptors in the PARATHYROID GLANDS play an important role in the maintenance of calcium HOMEOSTASIS by regulating the release of PARATHYROID HORMONE. They differ from INTRACELLULAR CALCIUM-SENSING PROTEINS which sense intracellular calcium levels.

A stromal interaction molecule that functions in the regulation of calcium influx following depletion of intracellular calcium in the ENDOPLASMIC RETICULUM. It translocates to the plasma membrane upon calcium depletion where it activates the CALCIUM RELEASE ACTIVATED CALCIUM CHANNEL ORAI1.

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