Departamento de Química y Bioquímica, Facultad de Farmacia, Universidad San Pablo-CEU, CEU Universities, Urbanización Montepríncipe, 28668 Boadilla del Monte, Spain.
Transplant Immunology Unit, National Center of Microbiology, Instituto de Salud Carlos III, 28220 Majadahonda, Spain.
Int J Mol Sci. 2023 May 20;24(10):9032. doi: 10.3390/ijms24109032.
The stimulator of interferon genes (STING) is an adaptor protein involved in the activation of IFN-β and many other genes associated with the immune response activation in vertebrates. STING induction has gained attention from different angles such as the potential to trigger an early immune response against different signs of infection and cell damage, or to be used as an adjuvant in cancer immune treatments. Pharmacological control of aberrant STING activation can be used to mitigate the pathology of some autoimmune diseases. The STING structure has a well-defined ligand binding site that can harbor natural ligands such as specific purine cyclic di-nucleotides (CDN). In addition to a canonical stimulation by CDNs, other non-canonical stimuli have also been described, whose exact mechanism has not been well defined. Understanding the molecular insights underlying the activation of STING is important to realize the different angles that need to be considered when designing new STING-binding molecules as therapeutic drugs since STING acts as a versatile platform for immune modulators. This review analyzes the different determinants of STING regulation from the structural, molecular, and cell biology points of view.
干扰素基因刺激物 (STING) 是一种衔接蛋白，参与 IFN-β 和许多其他与脊椎动物免疫反应激活相关基因的激活。STING 的诱导引起了不同角度的关注，例如有可能针对不同的感染和细胞损伤迹象触发早期免疫反应，或用作癌症免疫治疗的佐剂。异常 STING 激活的药理学控制可用于减轻某些自身免疫性疾病的病理学。STING 的结构具有明确的配体结合位点，可以容纳天然配体，如特定的嘌呤环二核苷酸 (CDN)。除了 CDN 的经典刺激外，还描述了其他非经典刺激，但其确切机制尚未很好地定义。了解 STING 激活的分子见解对于设计新的 STING 结合分子作为治疗药物时需要考虑的不同角度非常重要，因为 STING 作为免疫调节剂的多功能平台。本综述从结构、分子和细胞生物学的角度分析了 STING 调节的不同决定因素。
