IFT81-IFT74复合体在内运输过程中充当非传统的RabL2 GTPase激活蛋白
Niels Boegholm1, Narcis A Petriman1, Marta Loureiro-López2
1Department of Molecular Biology and Genetics, Aarhus University, Aarhus C, Denmark.
The EMBO journal
|August 22, 2023
概括
RabL2,一个小的GTPase,对于通过肌内运输 (IFT) 进行状细胞组合至关重要. IFT81/74的一个特定区域增强了RabL2.
科学领域:
- 细胞生物学 细胞生物学
- 分子生物学分子生物学
- 结构生物学 结构生物学
背景情况:
- 毛是参与细胞信号传递和运动的重要器官.
- 鞭毛体内传输 (IFT) 对于乳毛的构建和维护至关重要.
- RabL2,一个小的GTPase,在基体的IFT启动中发挥作用.
研究的目的:
- 为了阐明RabL2在IFT机器中融入的分子机制.
- 在IFT综合体内确定RabL2监管的结构基础.
- 了解RabL2-IFT相互作用对状运输的功能影响.
主要方法:
- 用CEP19和IFT组件净化和制RabL2的蛋白质.
- 在体外生化分析测量GTP水解速率.
- 结构建模和RabL2-IFT复合物的体外/细胞内验证.
主要成果:
- 一个含有IFT81/74的复合IFT复合物显著提高了RabL2的GTP水解率.
- 确定了IFT81/74的70个氨基酸卷轴区域作为促进RabL2 GTP水解的结合部位.
- 创建并验证了含有RabL2的IFT复合体的结构模型.
- 克拉米迪亚IFT81/74在增强人类RabL2 GTP水解方面表现出保守的活性.
结论:
- RabL2与IFT81/74的相互作用对于调节其GTPase活性至关重要.
- 这些发现提供了对RabL2在IFT综合体中的作用的架构理解.
- 这项研究为RabL2与IFT列车的及时分离提供了分子解释,确保了正确的纤毛功能.
相关概念视频
01:25Rab Cascades
2.7K
Rab GTPases act in a regulated cascade during membrane fusion, helping the lipid bilayers mix. The Rab family of proteins are active when bound to GTP, and inactive when bound to GDP. Hence, they act as guanine nucleotide-dependent molecular switches. Rab-GTP recognizes and binds to long or short-range tethering proteins to capture the target vesicle. These tethers coordinate with SNAREs on the vesicle and the target membrane to assemble the trans SNARE complex that locks the mixing bilayers.
2.7K
01:14Rab Proteins
4.0K
Rab proteins constitute the largest family of monomeric GTPases, of which 70 members are present in humans. Rab proteins and their effectors regulate consecutive stages of vesicle transport such as vesicle transport, docking, and fusion to the correct recipient membrane.
Rab proteins switch between a cytosolic, GDP-bound inactive state and a membrane-anchored, GTP-bound active state. By themselves, Rabs show slow rates of GDP/GTP exchange and GTP hydrolysis. Thus, Rab proteins are considered...
Rab proteins switch between a cytosolic, GDP-bound inactive state and a membrane-anchored, GTP-bound active state. By themselves, Rabs show slow rates of GDP/GTP exchange and GTP hydrolysis. Thus, Rab proteins are considered...
4.0K
01:20Cotranslational Protein Translocation
7.4K
Translocation of proteins across membranes is an ancient process that occurs even in bacteria and archaebacteria. In fact, the components of the translocation machinery are still conserved between prokaryotes and eukaryotes.
Sec61 channel partners for cotranslational translocation
During cotranslational translocation, the Sec61 channel partners with the signal recognition particle (SRP), the signal recognition particle receptor (SR), and the ribosomes to transport the nascent polypeptide chain...
Sec61 channel partners for cotranslational translocation
During cotranslational translocation, the Sec61 channel partners with the signal recognition particle (SRP), the signal recognition particle receptor (SR), and the ribosomes to transport the nascent polypeptide chain...
7.4K
01:28Protein Translocation Machinery on the ER Membrane
4.7K
The translocon complex situated on the ER membrane is the main gateway for the protein secretory pathway. It facilitates the transport of nascent peptides into the ER lumen and their insertion into the ER membrane.
Sec61 protein conducting channel
In eukaryotes, the translocon complex comprises a core heterotrimeric translocator channel called the Sec61 complex. This channel includes three transmembrane proteins, Sec61α, Sec61β, and Sec61γ, and is the largest subunit of the...
Sec61 protein conducting channel
In eukaryotes, the translocon complex comprises a core heterotrimeric translocator channel called the Sec61 complex. This channel includes three transmembrane proteins, Sec61α, Sec61β, and Sec61γ, and is the largest subunit of the...
4.7K
01:39Mechanism of Filopodia Formation
2.4K
Filopodia are thin, actin-rich cellular protrusions that play an important role in many fundamental cellular functions. They vary in their occurrence, length, and positioning in different cell types, suggesting their diverse roles.
Their main function is to guide migrating cells during normal tissue morphogenesis or cancer metastasis by recognizing and making initial contacts with the extracellular matrix. However, they can also act as stationary cell anchors or help to establish communication...
Their main function is to guide migrating cells during normal tissue morphogenesis or cancer metastasis by recognizing and making initial contacts with the extracellular matrix. However, they can also act as stationary cell anchors or help to establish communication...
2.4K
01:33Coat Assembly and GTPases
3.6K
Vesicles incorporate different coat protein subunits in different cell locations, which changes the properties of the coat, such as the shape and geometry of the transport vesicles. Thus, vesicle coat proteins also play a significant role in cargo selection.
Coat assembly depends on the local availability of phosphatidylinositol phosphates or PIPs and GTP-binding proteins. Adaptor proteins, which link the coat proteins to the membrane, bind to these PIPs and play a crucial role in controlling...
Coat assembly depends on the local availability of phosphatidylinositol phosphates or PIPs and GTP-binding proteins. Adaptor proteins, which link the coat proteins to the membrane, bind to these PIPs and play a crucial role in controlling...
3.6K