Pore properties of Orai1 calcium channel dimers and their activation by the STIM1 ER calcium sensor.

ABSTRACT: Store-operated Ca²⁺ entry signals are mediated by plasma membrane Orai channels activated through intermembrane coupling with Ca²⁺-sensing STIM proteins in the endoplasmic reticulum (ER). The nature of this elaborate Orai-gating mechanism has remained enigmatic. Based on the Drosophila Orai structure, mammalian Orai1 channels are hexamers comprising three dimeric subunit pairs. We utilized concatenated Orai1 dimers to probe the function of key domains within the channel pore and gating regions. The Orai1-E106Q selectivity-filter mutant, widely considered a dominant pore blocker, was surprisingly nondominant within concatenated heterodimers with Orai1-WT. The Orai1-E106Q/WT heterodimer formed STIM1-activated nonselective cation channels with significantly enlarg

SUBMITTER: Cai X 

PROVIDER: S-EPMC6102135 | biostudies-literature | 2018 Aug

REPOSITORIES: biostudies-literature