定义西格玛1受体的依赖于连接体的近似组
Jing Zhao1,2, Rajalakshmi Veeranan-Karmegam3, Frederick C Baker3
1Department of Ophthalmology, Medical College of Georgia at Augusta University, Augusta, GA, United States.
Frontiers in cell and developmental biology
|June 23, 2023
概括
西格玛1受体 (S1R) 作为分子伴侣,与200多种蛋白质相互作用,影响分泌和胆固醇通路. 干结合改变了这些相互作用,为S1R揭示了新的治疗潜力.
科学领域:
- 细胞生物学 细胞生物学
- 分子生物学分子生物学
- 生物化学 生物化学
背景情况:
- 西格玛1受体 (S1R) 是一种多功能治疗点,涉及多种疾病,包括神经退行,癌症和COVID-19.
- S1R是无处不在的表达和提出作为一个依赖于连接体的分子伴侣调节细胞内信号的功能.
- 了解S1R的互动组对于阐明其多样化的生物作用至关重要.
研究的目的:
- 在本地条件下全面绘制Sigma 1受体近似组图.
- 研究如何在与特定的激动剂和抗剂结合时S1R互动组的变化.
- 为了确定新的S1R相互作用蛋白和途径.
主要方法:
- 通过将Apex2结合酶与S1R.结合,利用了依赖近距离的生物化 (BioID).
- 采用定量质谱法在S1R-Apex表达细胞中识别生物化蛋白质.
- 在原生条件下和在S1R配体的存在下分析了蛋白质相互作用.
主要成果:
- 在本地条件下识别了200多种新的S1R相互作用蛋白,其中许多参与了分泌途径.
- 观察到与分泌,细胞外基质形成和胆固醇生物合成相关的蛋白质的依赖联体的丰富.
- 证明了PCSK9和LDLR对S1R的改变结合,以应对特定的S1R抗剂和激动剂.
- 展示了与细胞分泌物的变化相关的联结S1R状态.
结论:
- 该研究定义了S1R近似基因组,揭示了新的相互作用和功能.
- 结果支持S1R作为细胞内伴侣的作用,在分泌和胆固醇代谢中发挥重要作用.
- 这些发现为S1R在各种病理状况的治疗潜力提供了新的见解.
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