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Updated: Dec 27, 2025

Targeting Cysteine Thiols for in Vitro Site-specific Glycosylation of Recombinant Proteins
Published on: October 4, 2017
STIM1 interacts with termini of Orai channels in a sequential manner
Liling Niu1,2, Fuyun Wu2,3, Kaili Li4
1Department of Immunology, School of Basic Medical Sciences, Tianjin Medical University, and Tianjin Key Laboratory of Cellular and Molecular Immunology, Tianjin 300070, China.
Abstract:
Store-operated Ca2+ entry (SOCE) is critical for numerous Ca2+-related processes. The activation of SOCE requires engagement between stromal interaction molecule 1 (STIM1) molecules on the endoplasmic reticulum and Ca2+ release-activated channel (CRAC) Orai on the plasma membrane. However, the molecular details of their interactions remain elusive. Here, we analyzed STIM1-Orai interactions using synthetic peptides derived from the N- and C-termini of Orai channels (Orai-NT and Orai-CT, respectively) and purified fragments of STIM1. The binding of STIM1 to Orai-NT is hydrophilic based, whereas binding to the Orai-CT is mostly hydrophobic. STIM1 decreases its affinity for Orai-CT when Orai-NT is present, supporting a stepwise interaction. Orai3-CT exhibits stronger binding to STIM1 than Orai1-CT, largely due to the shortness of one helical turn. The role of newly identified residues was confirmed by co-immunoprecipitation and Ca2+ imaging using full-length molecules. Our results provide important insight into CRAC gating by STIM1.
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