Influx of @entity141 through store-operated @entity141 channels (SOCs) is a central component of receptor-evoked @entity141 signals. Orai channels are SOCs that are gated by @entity7010 , a @entity141 sensor located in the ER but how it gates and regulates the Orai channels is unknown. Here, we report the molecular basis for gating of Orais by @entity7010 . All Orai channels are fully activated by the conserved @entity7010 @entity535 fragment 344-442, which we termed SOAR (the @entity7010 Orai activating region). SOAR acts in combination with @entity7010 (450-485) to regulate the strength of interaction with @entity7011 . Activation of @entity7011 by SOAR recapitulates all the kinetic properties of @entity7011 activation by @entity7010 . However, mutations of @entity7010 within SOAR prevent activation of @entity7011 but not co-clustering of @entity7010 and @entity7011 in response to @entity141 store depletion, indicating that @entity7010 - @entity7011 co-clustering is not sufficient for @entity7011 activation. An intact @entity1473 terminus alpha-helicial region of Orai is required for activation by SOAR. Deleting most of the @entity7011 @entity1472 terminus impaired @entity7011 activation by @entity7010 , but @entity7011 (Delta1-73) interacted with and was fully activated by SOAR. Accordingly, the characteristic inward rectification of Orai is mediated by an interaction between the polybasic @entity7010 (672-685) and a Pro-rich region in the N terminus of @entity7011 . Hence, the essential properties of @entity7011 function can be rationalized by interactions with discrete regions of @entity7010 .

SOAR and the polybasic XXXX domains gate and regulate Orai channels.

@entity1472 :: ('CHEBI:46882', 'Chemical') :: ['amino'] @entity7010 :: ('6786', 'Gene') :: ['STIM1'] @entity535 :: ('CHEBI:33704', 'Chemical') :: ['amino acid'] @entity7011 :: ('84876', 'Gene') :: ['Orai1'] @entity141 :: ('CHEBI:29108', 'Chemical') :: ['Ca(2+)'] @entity1473 :: ('CHEBI:46883', 'Chemical') :: ['carboxy']
@entity7010 :: (6786,Gene) :: ['STIM1']
