Secretory Physiology Section, National Institute of Dental and Craniofacial Research, National Institutes of Health, Bethesda, MD 20892-1190, USA.
Biomolecules. 2024 Sep 24;14(10):1200. doi: 10.3390/biom14101200.
Calcium is an important second messenger that is involved in almost all cellular processes. Disruptions in the regulation of intracellular Ca levels ([Ca]) adversely impact normal physiological function and can contribute to various diseased conditions. STIM and Orai proteins play important roles in maintaining [Ca] through store-operated Ca entry (SOCE), with STIM being the primary regulatory protein that governs the function of Orai channels. STIM1 and STIM2 are single-pass ER-transmembrane proteins with their N- and C-termini located in the ER lumen and cytoplasm, respectively. The N-terminal EF-SAM domain of STIMs senses [Ca] changes, while the C-terminus mediates clustering in ER-PM junctions and gating of Orai1. ER-Ca store depletion triggers activation of the STIM proteins, which involves their multimerization and clustering in ER-PM junctions, where they recruit and activate Orai1 channels. In this review, we will discuss the structure, organization, and function of EF-hand motifs and the SAM domain of STIM proteins in relation to those of other eukaryotic proteins.
钙是一种重要的第二信使，几乎参与所有细胞过程。细胞内钙水平([Ca])调节紊乱会对正常生理功能产生不利影响，并可能导致各种疾病状态。STIM 和 Orai 蛋白在通过储存操纵的钙内流（SOCE）维持[Ca]方面发挥重要作用，其中 STIM 是调节 Orai 通道功能的主要调节蛋白。STIM1 和 STIM2 是单次跨膜 ER 蛋白，其 N 端和 C 端分别位于 ER 腔和细胞质中。STIM 的 N 端 EF-SAM 结构域感知[Ca]变化，而 C 端介导 ER-PM 连接点的聚集和 Orai1 的门控。ER 钙储存耗竭触发 STIM 蛋白的激活，涉及它们在 ER-PM 连接点的多聚化和聚集，在那里它们招募和激活 Orai1 通道。在这篇综述中，我们将讨论 EF 手结构域和 STIM 蛋白的 SAM 结构域与其他真核蛋白的结构、组织和功能的关系。
