An effective get-together

Cesari, Francesca

doi:10.1038/nrm2540

Research Highlight
Published: November 2008

Calcium

An effective get-together

Francesca Cesari

Nature Reviews Molecular Cell Biology volume 9, page 824 (2008)Cite this article

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The activity of CRAC channels relies on the ER transmembrane protein stromal interaction molecule-1 (STIM1), which senses the depletion of Ca²⁺ in the ER and physically relays this information to the plasma membrane protein ORAI1, which forms the pore of the Ca²⁺ channel.

Using nuclear magnetic resonance (NMR), Stathopulos et al. determined the three-dimensional atomic structure of the Ca²⁺-sensing region of STIM1, which consists of the EF-hand and sterile α-motif (SAM) domains (EF–SAM domains). They found a 'hidden' EF-hand domain that stabilizes the EF–SAM intramolecular interaction. Mutations that alter the structure of the SAM, EF-hand or hidden EF-hand domains unfold the EF–SAM domain and disrupt Ca²⁺ sensitivity. Furthermore, they induce Ca²⁺ flux independently of the ER Ca²⁺ store. So, the conformation of the STIM1 Ca²⁺-sensing region is crucial for store-operated Ca²⁺ entry.

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ORIGINAL RESEARCH PAPERS

Penna, A. et al. The CRAC channel consists of a tetramer formed by Stim-induced dimerization of Orai dimers. Nature 28 Sept 2008 (doi: 10.1038/nature07338)
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Stathopulos, P. B. et al. Structural and mechanistic insights into STIM1-mediated initiation of store-operated calcium entry. Cell 135, 110–122 (2008)
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