货物选择性囊泡结合:由戈尔吉结合元件结合特定货物蛋白的结构基础 TBC1D2323
Jérôme Cattin-Ortolá1, Jonathan G G Kaufman2, Alison K Gillingham1
1MRC Laboratory of Molecular Biology, Francis Crick Avenue, Cambridge CB2 0QH, UK.
Science advances
|March 29, 2024
概括
蛋白质TBC1D23通过一种新的机制捕获了内体到戈尔吉运输囊泡. 它可以识别货物蛋白质上的特定酸性图案,确保准确的传送到戈尔吉装置.
科学领域:
- 细胞生物学 细胞生物学
- 分子生物学分子生物学
- 贩卖蛋白质 贩卖蛋白质 是一个问题.
背景情况:
- 高尔基局部化的高尔基蛋白 (高尔基-97和高尔基-245) 从内分体中捕获运输囊泡.
- 蛋白质TBC1D23介导这种捕获,其N端域结合高尔金和C端域结合囊泡.
研究的目的:
- 阐明TBC1D23的炭基终端域识别和捕获特定的内体衍生运输囊泡的机制.
主要方法:
- 酵母双杂交查,以确定TBC1D23的碳素终端域的结合伙伴.
- 同免疫沉和体外结合试验.
- 进行X射线晶体学以确定结合界面.
- 在基于细胞的测试中以结构为导向的突变发生.
主要成果:
- TBC1D23的碳素终端域直接结合碳氧酶D和合成素-16,已知的囊泡载荷蛋白.
- 结合是通过这些货物蛋白中存在的保存酸性三氨酸-氨酸-氨酸 (TLY) 基因发生的.
- 晶体结构揭示了酸性TLY动机与TBC1D23.23之间的详细相互作用.
- 破坏TLY动机结合的突变在体内取消了囊泡捕获.
结论:
- TBC1D23采用了一种以前未被描述的囊泡捕获机制,在内体到戈尔吉载荷蛋白上识别了一个共享的酸性TLY动机.
- 这种图案识别可以确保货物的具体和高效的交付到Golgi装置.
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