{"database":"biostudies-literature","file_versions":[],"scores":null,"additional":{"submitter":["Yu T"],"funding":["National Natural Sciences Foundation of China"],"pagination":["e202201623"],"full_dataset_link":["https://www.ebi.ac.uk/biostudies/studies/S-EPMC9873985"],"repository":["biostudies-literature"],"omics_type":["Unknown"],"volume":["6(4)"],"pubmed_abstract":["Store-operated Ca<sup>2+</sup> entry (SOCE) is a universal Ca<sup>2+</sup> influx pathway that is important for the function of many cell types. SOCE is controlled by the interaction of the ER Ca<sup>2+</sup> sensor STIM1 with the plasma membrane Ca<sup>2+</sup> channel Orai1. S417 is located in the third coiled-coil (CC3) domain of the C-terminus of STIM1. We found that single-point mutation of this residue (S417G) abolished STIM1 C-terminus interactions with Orai1. Mutation of S417 also abolished CAD-Orai1 binding and Orai1 channel activation, eliminated STIM1 puncta formation, and co-localization with Orai1 and SOCE. 2-APB was found to restore the binding of the STIM1 C-terminus mutant (S417G) to Orai1 and dose-dependently activate Orai1 channel. Both CBD and NBD of Orai1 are required for 2-APB-induced coupling between the Orai1 and STIM1 C-terminus mutant (S417G) and CRAC channel activation. We also demonstrated that 2-APB led to delayed activation of Orai1-K85E channel, although Orai1-K85E obviously impairs 2-APB-induced STIM1 C-terminus mutant (S417G)-Orai1 coupling. Our results suggest S417 in the CC3 domain of STIM1 is essential for STIM1-Orai1 binding and CRAC channel activation."],"journal":["Life science alliance"],"pubmed_title":["S417 in the CC3 region of STIM1 is critical for STIM1-Orai1 binding and CRAC channel activation."],"pmcid":["PMC9873985"],"funding_grant_id":["30871311","31371217"],"pubmed_authors":["Liu H","Li X","Luo Q","Li S","He J","Yu T","Jin J"],"additional_accession":[]},"is_claimable":false,"name":"S417 in the CC3 region of STIM1 is critical for STIM1-Orai1 binding and CRAC channel activation.","description":"Store-operated Ca<sup>2+</sup> entry (SOCE) is a universal Ca<sup>2+</sup> influx pathway that is important for the function of many cell types. SOCE is controlled by the interaction of the ER Ca<sup>2+</sup> sensor STIM1 with the plasma membrane Ca<sup>2+</sup> channel Orai1. S417 is located in the third coiled-coil (CC3) domain of the C-terminus of STIM1. We found that single-point mutation of this residue (S417G) abolished STIM1 C-terminus interactions with Orai1. Mutation of S417 also abolished CAD-Orai1 binding and Orai1 channel activation, eliminated STIM1 puncta formation, and co-localization with Orai1 and SOCE. 2-APB was found to restore the binding of the STIM1 C-terminus mutant (S417G) to Orai1 and dose-dependently activate Orai1 channel. Both CBD and NBD of Orai1 are required for 2-APB-induced coupling between the Orai1 and STIM1 C-terminus mutant (S417G) and CRAC channel activation. We also demonstrated that 2-APB led to delayed activation of Orai1-K85E channel, although Orai1-K85E obviously impairs 2-APB-induced STIM1 C-terminus mutant (S417G)-Orai1 coupling. Our results suggest S417 in the CC3 domain of STIM1 is essential for STIM1-Orai1 binding and CRAC channel activation.","dates":{"release":"2023-01-01T00:00:00Z","publication":"2023 Apr","modification":"2026-05-10T06:59:34.073Z","creation":"2025-02-18T23:45:09.583Z"},"accession":"S-EPMC9873985","cross_references":{"pubmed":["36690443"],"doi":["10.26508/lsa.202201623"]}}