Biomolecular condensates (biocondensates) formed via liquid–liquid phase-separation of soluble proteins have been studied extensively. However, neither the phase-separation of endoplasmic reticulum (ER) transmembrane protein nor a biocondensate with organized membranous structures has been reported. Here, we have discovered a spherical ER membranous biocondensate with puzzle-like structures caused by condensation of the ER-resident stimulator of interferon genes (STING) in DNA virus-infected or 2′3′-cGAMP (cyclic GMP-AMP)-treated cells, which required STING transmembrane domains, an intrinsically disordered region (IDR) and a dimerization domain. Intracellular 2′3′-cGAMP concentrations determined STING translocation or condensation. STING biocondensates constrained STING and TBK1 (TANK binding protein 1) to prevent innate immunity from overactivation, presumably acting like a ‘STING-TBK1-cGAMP sponge’. Cells expressing STING-E³³⁶G/E³³⁷G showed notably enhanced innate immune responses due to impaired STING condensation after viral infection at later stages. Microtubule inhibitors impeded the STING condensate gel-like transition and augmented type I-interferon production in DNA virus-infected cells. This membranous biocondensate was therefore named the STING phase-separator.

通过可溶性蛋白质的液-液相分离形成的生物分子凝聚物（生物凝聚物）已被广泛研究。然而，内质网 (ER) 跨膜蛋白的相分离和具有组织化膜结构的生物凝结物均未见报道。在这里，我们发现了一种球形 ER 膜生物凝聚物，具有拼图样结构，这是由 DNA 病毒感染或 2'3'-cGAMP（环 GMP-AMP）处理的 ER 干扰素基因刺激物（STING）凝聚引起的细胞，这需要 STING 跨膜结构域、一个本质上无序的区域 (IDR) 和一个二聚化结构域。细胞内 2'3'-cGAMP 浓度决定了 STING 易位或凝聚。STING 生物凝结物限制 STING 和 TBK1（TANK 结合蛋白 1）以防止先天免疫过度激活，大概就像“STING-TBK1-cGAMP 海绵”一样。表达 STING-E 的细胞³³⁶ G/E ³³⁷ G 由于后期病毒感染后 STING 凝聚受损，显示出显着增强的先天免疫反应。微管抑制剂阻碍了 DNA 病毒感染细胞中的 STING 凝结凝胶样转变和增加 I 型干扰素的产生。因此，这种膜状生物冷凝物被命名为 STING 相分离器。