Coiled-Coil Formation Conveys a STIM1 Signal from ER Lumen to Cytoplasm

• DOI: 10.1016/j.celrep.2017.12.030
• Publication Date: 2018-01-02T16:41:43Z
• Authors: Nupura Hirve; Vangipurapu Rajan...; Patrick G. Hogan; Aparna Gudlur
• Keywords: Orai1; Conformational change; Coiled coil; ER retention

STIM1 and STIM2 are endoplasmic reticulum (ER) membrane proteins that sense decreases in ER-luminal free Ca2+ and, through a conformational change the STIM cytoplasmic domain, control gating of plasma channel ORAI1. To determine how conveys signal from ER lumen to cytoplasm, we studied Ca2+-dependent engineered isolated membranes parallel, physiological activation these cells. We find conserved "sentinel" features CC1 region help prevent while is bound domains. Reduced drives concerted change, which luminal domains rearrange transmembrane helices initial parts regions pair an extended coiled coil. This intradimer rearrangement overcomes relatively weak CC1-SOAR/CAD interactions hold inactive conformation, releasing SOAR/CAD domain activate ORAI channels.