ReviewStore operated calcium entry: From concept to structural mechanisms

•STIM and Orai proteins mediate J.W. Putney's store operated calcium entry.•The STIM luminal EFSAM domains sense stored calcium depletion.•The STIM cytosolic domains couple to and gate plasma membrane Orai channels.

In 1986, J.W. Putney presented a model for capacitative calcium (Ca2+) entry conveying that depletion of endoplasmic reticulum stored Ca2+ levels leads to activation of plasma membrane Ca2+ channels which mediate influx of Ca2+ from the extracellular space into cells. Presently, the biomolecules regulating this process, more widely known as store operated Ca2+ entry (SOCE) which is vital to myriad signaling pathways in health and disease, are known and the focus of intense structural biology research aiming to illuminate the atomic mechanisms of function. This brief review highlights the known structures with respect to the mechanisms of SOCE regulation and possible future directions in this field developed out of Putney's conceptualization of this process.

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