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化EM在治疗刺痛的药物开发中的应用

Xiao-Chen Bai¹, Xuewu Zhang²

¹Department of Biophysics, University of Texas Southwestern Medical Center, Dallas, TX 75390, USA.

Current opinion in structural biology

|January 6, 2024

概括

刺蛋白是cGAS-STING免疫通路中的关键. 化EM研究揭示了STING是如何激活的,为癌症和自身免疫性疾病提供了新的治疗点.

科学领域:

免疫学免疫学免疫学
结构生物学结构生物学
生物化学生物化学

背景情况:

STING (干扰素基因刺激器) 是cGAS-STING先天免疫通路中的一个关键的适应蛋白.
循环GMP-AMP (cGAMP) 激活STING会导致下游免疫反应.
对cGAS-STING通路的失调与各种疾病有关,包括癌症和自身免疫性疾病.

研究的目的:

通过使用冷电子显微镜 (cryo-EM) 突出了解STING的调节机制的最新进展.
探索cGAMP模拟物和与STING结合的新型小分子带的作用机制.
确定调节STING活动的潜在治疗策略.

主要方法:

使用冷电子显微镜 (cryo-EM) 来确定STING的结构.
分析STING与循环GMP-AMP (cGAMP) 模仿剂和小分子接体复合的分析.

主要成果:

化EM结构揭示了在带结合时STING激活的分子基础.
这些研究阐明了STING的各种小分子调节器的作用机制.
结构性见解表明了针对cGAS-STING通路的治疗干预的新方法.

结论:

STING是免疫相关疾病的验证治疗点.
化电磁器显著提高了对STING调节的结构性理解.
新型小分子配体为调节STING活性以获得治疗益处提供了有希望的途径.

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Cryo-electron Microscopy

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Conventional electron microscopy (EM) involves dehydration, fixation, and staining of biological samples, which distorts the native state of biological molecules and results in several artifacts. Also, the high-energy electron beam damages the sample and makes it difficult to obtain high-resolution images. These issues can be addressed using cryo-EM, which uses frozen samples and gentler electron beams. The technique was developed by Jacques Dubochet, Joachim Frank, and Richard Henderson, for...