Calcium sensing by the STIM1 ER-luminal domain.

ABSTRACT: Stromal interaction molecule 1 (STIM1) monitors ER-luminal Ca²⁺ levels to maintain cellular Ca²⁺ balance and to support Ca²⁺ signalling. The prevailing view has been that STIM1 senses reduced ER Ca²⁺ through dissociation of bound Ca²⁺ from a single EF-hand site, which triggers a dramatic loss of secondary structure and dimerization of the STIM1 luminal domain. Here we find that the STIM1 luminal domain has 5-6 Ca²⁺-binding sites, that binding at these sites is energetically coupled to binding at the EF-hand site, and that Ca²⁺ dissociation controls a switch to a second structured conformation of the luminal domain rather than protein unfolding. Importantly, the other luminal-domain Ca²⁺-binding sites in

SUBMITTER: Gudlur A 

PROVIDER: S-EPMC6208404 | biostudies-literature | 2018 Oct

REPOSITORIES: biostudies-literature