The STIM1 CTID domain determines access of SARAF to SOAR to regulate Orai1 channel function.

ABSTRACT: Ca(2+) influx by store-operated Ca(2+) channels (SOCs) mediates all Ca(2+)-dependent cell functions, but excess Ca(2+) influx is highly toxic. The molecular components of SOC are the pore-forming Orai1 channel and the endoplasmic reticulum Ca(2+) sensor STIM1. Slow Ca(2+)-dependent inactivation (SCDI) of Orai1 guards against cell damage, but its molecular mechanism is unknown. Here, we used homology modeling to identify a conserved STIM1(448-530) C-terminal inhibitory domain (CTID), whose deletion resulted in spontaneous clustering of STIM1 and full activation of Orai1 in the absence of store depletion. CTID regulated SCDI by determining access to and interaction of the STIM1 inhibitor SARAF with STIM1 Orai1 activation region (SOAR), the STIM1 domain that activates Orai1. CTID had two lobe

SUBMITTER: Jha A 

PROVIDER: S-EPMC3704993 | biostudies-literature | 2013 Jul

REPOSITORIES: biostudies-literature