DNAJC13对内分体的定位受到其J域及其无序的C端尾尾部的反对
Hayden Adoff1, Brandon Novy1, Emily Holland1
1Department of Chemical Physiology and Biochemistry, Oregon Health & Science University, Portland, OR 97239, USA.
bioRxiv : the preprint server for biology
|January 7, 2025
概括
DNAJC13蛋白在内分体的局部化是由其J域和C终端尾部调节的. 这些区域对其PH类域有负面控制,影响了内体体贩运通路.
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:
- 内分泌体是细胞膜蛋白质的关键分类中心.
- DNAJC13 (也称为RME-8) 对于将蛋白质引导到循环或降解途径至关重要.
- DNAJC13的N端Plekstrin同质性 (PH) 类域介导其结合到内体酸-3-酸盐 (PI(3) P).
研究的目的:
- 研究控制DNAJC13局部化到内分泌体的调控机制.
- 在DNAJC13中确定调节其内体向的特定区域和动机.
- 要阐明DNAJC13与PI(3) P的相互作用是如何调节的.
主要方法:
- DNAJC13域的结构功能分析.
- 定量蛋白质组学来绘制监管区域的地图.
- 保存动机的局部定向突变发生 (YLT和HPD).
- 细胞局部化试验和体外PI(3) P结合实验.
主要成果:
- DNAJC13的J域和C终端尾部作为其PH类域的负调节者.
- 保存的YLT基因 (C端尾) 和HPD三位体 (J域) 中的突变增强了DNAJC13内体局部化.
- 这些突变还增加了DNAJC13在体外对PI(3) P的结合亲和力.
- 有效的PI(3) P结合和内局部化取决于DNAJC13的寡合化,而不仅仅是孤立的PH类域.
结论:
- DNAJC13局部化到内分泌体是通过分子内相互作用严格控制的.
- J域和C端尾作为抑制元素,防止过早或过度的PI(3) P结合.
- 对于PH类域来说,寡合化是必不可少的,以实现高亲和度PI(3) P结合和适当的内体向.
- 这项研究揭示了调节DNAJC13在内体贩运中的作用的分子机制.
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