Abstract
Store-operated Ca2+ entry (SOCE) is a critical Ca2+ signaling pathway in many cell types. After sensing Ca2+ store depletion in the endoplasmic reticulum (ER) lumen, STIM1 (STromal Interaction Molecule 1) oligomerizes and then interacts with and activates the Orai1 calcium channel. Our previous research has demonstrated that the inhibitory helix (IH) adjacent to the first coiled-coil region (CC1) of STIM1 may keep the whole C-terminus of STIM1 in an inactive state. However, the specific conformational change of CC1-IH that drives the transition of STIM1 from the resting state to the active state remains elusive. Herein, we report the structural analysis of CC1-IH, which revealed that the entire CC1-IH molecule forms a very long helix. Structural and biochemical analyses indicated that IH, and not the CC1 region, contributes to the oligomerization of STIM1. Small-angle X-ray scattering (SAXS) analysis suggested that the C-terminus of STIM1 including the IH region displays a collapsed conformation, whereas the construct without the IH region has an extended conformation. These two conformations may correspond to the conformational states of the C-terminus of STIM1 before and after activation. Taken together, our results provide direct biochemical evidence that the IH region controls the conformational switching of the C-terminus of STIM1.
Highlights
Calcium (Ca2+) signaling plays a critical role in the regulation of various physiological processes [1]
Two protein families are involved in this signaling pathway: the endoplasmic reticulum (ER)-localized stromal interaction molecule (STIM) calcium sensors [4,5] and the calcium-release activated calcium (CRAC) channels, which are located in the plasma membrane [6,7,8]
There are four CC1-inhibitory helix (IH)-mut molecules in one asymmetric unit (Figure 1B), and each molecule consists of an elongated α-helix stretching from its N-terminal end to its C-terminal end
Summary
Calcium (Ca2+) signaling plays a critical role in the regulation of various physiological processes [1]. Two protein families are involved in this signaling pathway: the ER-localized stromal interaction molecule (STIM) calcium sensors [4,5] and the calcium-release activated calcium (CRAC) channels (consisting of Orai family proteins), which are located in the plasma membrane [6,7,8]. A series of cellular events are triggered following extracellular ligand binding to phospholipase C (PLC)coupled receptors on the plasma membrane [10,11,12]. These events result in Ca2+ release from the ER lumen. Constitutive Ca2+ entry is achieved through the opening of CRAC channels, which further elicits intracellular Ca2+ signals and replenishes the depleted Ca2+ stores in the ER lumen [1,2,3]
Sign-in/Register to view highlights & summary Sign-in/Register to access full text options 
Talk to us
Join us for a 30 min session where you can share your feedback and ask us any queries you have
Schedule a callDisclaimer: All third-party content on this website/platform is and will remain the property of their respective owners and is provided on "as is" basis without any warranties, express or implied. Use of third-party content does not indicate any affiliation, sponsorship with or endorsement by them. Any references to third-party content is to identify the corresponding services and shall be considered fair use under The CopyrightLaw.
