Orai3 - the ‘exceptional’ Orai?

Communication between N terminus and loop2 tunes Orai activation

Ca2+ release-activated Ca2+ (CRAC) channels constitute the major Ca2+ entry pathway into the cell. They are fully reconstituted via intermembrane coupling of the Ca2+-selective Orai channel and the Ca2+-sensing protein STIM1. In addition to the Orai C terminus, the main coupling site for STIM1, the Orai N terminus is indispensable for Orai channel gating. Although the extended transmembrane Ora...

The STIM1/Orai signaling machinery

Ca(2+) influx via store-operated Ca(2+) release activated Ca(2+) (CRAC) channels represents a main signaling pathway for T-cell activation as well as mast-cell degranulation. The ER-located Ca(2+)-sensor, STIM1 and the Ca(2+)-selective ion pore, Orai1 in the membrane are sufficient to fully reconstitute CRAC currents. Their identification, but even more the recent structural resolution of both ...

CRACking the structure of Orai

Correspondence to: Andrew P. Braun Email: [email protected] Calcium (Ca) is well recognized as a key second messenger in a variety of eukaryotic signal transduction pathways, and nature has developed a number of regulatory mechanisms to mediate its cellular influx and efflux and its homeostasis within the cell. Stimulus-evoked release of Ca stored within internal organelles (i.e., endoplasmic ...

The many faces of Orai.

Molecular Determinants within N Terminus of Orai3 Protein That Control Channel Activation and Gating*

STIM1 and Orai represent the key components of Ca(2+) release-activated Ca(2+) channels. Activation of Orai channels requires coupling of the C terminus of STIM1 to the N and C termini of Orai. Although the latter appears to be central in the interaction with STIM1, the role of the N terminus and particularly of the conserved region close to the first transmembrane sequence is less well underst...