人类STING通过一种类似的分子化合物被激活
Jie Li1, Stephen M Canham2, Hua Wu3
1Department of Biophysics, University of Texas Southwestern Medical Center, Dallas, TX, USA.
Nature chemical biology
|October 12, 2023
概括
研究人员发现了NVS-STG,这些化合物激活了干扰基因刺激器 (STING) 蛋白. NVS-STG2充当分子剂,诱导用于免疫反应和抗瘤活性的STING寡合化.
科学领域:
- 免疫学 免疫学 免疫学
- 结构生物学 结构生物学
- 药物发现 药物发现 药物发现
背景情况:
- 干扰素基因刺激器 (STING) 对于先天免疫非常重要,具有抗瘤潜力.
- STING激活需要高阶寡合化,通常由联体cGAMP诱导.
- 向STING提供了针对感染和癌症的治疗策略.
研究的目的:
- 为了发现能激活人类刺痛的新型化合物.
- 阐明这些化合物激活STING的机制.
- 评估STING激活化合物的治疗潜力.
主要方法:
- 功能性查以确定STING激活器.
- 低温电子显微镜 (cryo-EM) 用于确定结构机制.
- 基于细胞的测试来评估免疫反应.
- 动物模型用于评估抗瘤活性.
主要成果:
- 发现了一种名为NVS-STG的新型STING激活剂.
- NVS-STG2通过在相邻的STING二次体的跨膜域之间结合来诱导STING高阶寡合化.
- 在体外,NVS-STG2表现出强大的STING介导的免疫激活,在体内表现出强大的抗瘤作用.
结论:
- 在NVS-STG2的功能中,NVS-STG2作为分子接剂来激活STING.
- 这一发现为基于STING的免疫疗法提供了一种新的化学模式.
- 在治疗癌症和传染病方面,NVS-STGs具有前景.
相关概念视频
Intracellular Signaling Affects Focal Adhesions
2.7K
Integrins act both as extracellular input receivers and as intracellular processing activators. As their name suggests, integrins are entirely integrated into the membrane structure. Their hydrophobic membrane-spanning regions interact with the phospholipid bilayer's hydrophobic region. These membrane receptors provide extracellular attachment sites for effectors like hormones and growth factors. They activate intracellular response cascades when their effectors are bound and active.
Some...
Some...
2.7K
Activation of Integrins
3.5K
Integrins bind ligands and transmit information from outside the cell to inside or vice-versa through an "outside-in signaling" or "inside-out signaling."
In "outside-in signaling," external factors in the extracellular space bind to exposed ligand binding sites on integrins. This causes the inactive protein to undergo a conformational change to become active. Integrins are often clustered on the cell membrane. Repetitive and regularly spaced ligand binding...
In "outside-in signaling," external factors in the extracellular space bind to exposed ligand binding sites on integrins. This causes the inactive protein to undergo a conformational change to become active. Integrins are often clustered on the cell membrane. Repetitive and regularly spaced ligand binding...
3.5K
The JAK-STAT Signaling Pathway
8.9K
Several cytokine receptors have tightly bound Janus kinase or JAK proteins attached at their cytosolic tail. Small signaling molecules such as cytokines, growth hormones, or prolactins bind to the cytokine receptors and initiate their dimerization. The dimerization brings the cytosolic JAKs together that trans-phosphorylate and activates each other. The activated JAKs now phosphorylate cytosolic tails of the cytokine receptors, which serve as binding sites for adaptor proteins such as SH2...
8.9K
IP3/DAG Signaling Pathway
12.1K
Membrane lipids such as phosphatidylinositol (PI) are precursors for several membrane-bound and soluble second messengers. Specific kinases phosphorylate PI and produce phosphorylated inositol phospholipids. One such inositol phospholipids are the phosphatidylinositol-4,5 bisphosphate [PI(4,5)P2], present in the inner half of the lipid bilayer. Upon ligand binding, GPCR stimulates Gq proteins to turn on phospholipase Cꞵ. Activated phospholipase Cꞵ cleaves PI(4,5)P2 and...
12.1K
GPCRs Regulate Adenylyl Cylase Activity
5.6K
Some GPCRs transmit signals through adenylyl cyclase (AC), a transmembrane enzyme. AC helps synthesize second messenger cyclic adenosine monophosphate (cAMP). AC catalyzes cyclization reaction and converts ATP to cAMP by releasing a pyrophosphate. The pyrophosphate is further hydrolyzed to phosphate by the enzyme pyrophosphatase, which drives cAMP synthesis to completion. However, cAMP is rapidly degraded to 5′ AMP by the enzymes phosphodiesterase (PDE), preventing overstimulation of...
5.6K


