通过蛋白质胆转移酶调节Rab GTPase的功能
Shaeri Mukherjee1, Xiaoyun Liu, Kohei Arasaki
1Section of Microbial Pathogenesis, Yale University School of Medicine, Boyer Center for Molecular Medicine, Yale University, New Haven, Connecticut, CT 06536, USA.
Nature
|August 9, 2011
概括
莱吉欧内拉肺菌通过使用新型的基化来修改宿主细胞GTPases. 这种细菌策略通过准Rab GTPases来改变宿主细胞功能,影响膜运输通路.
科学领域:
- 微生物学 微生物学
- 细胞生物学 细胞生物学
- 生物化学 生物化学
背景情况:
- 细胞内病原体,如莱吉欧内拉肺炎菌操纵宿主细胞的GTPases.
- 众所周知,Legionella蛋白,如DrrA,可以通过AMPylation修改像Rab1这样的GTPase.
研究的目的:
- 通过质谱测量,研究在莱吉欧内拉感染期间Rab1的翻译后修改.
- 确定参与宿主细胞调节的新型细菌效应蛋白和机制.
主要方法:
- 质谱法用于分析感染期间宿主细胞蛋白质的修饰.
- 生物化学测试以表征蛋白质与蛋白质相互作用和酶活性.
- 在体外研究中使用纯化的蛋白质和基质.
主要成果:
- 在军团菌感染期间证实了Rab1的DrrA介导的AMPylation.
- 发现了一种新奇的,DrrA独立的Rab1修饰由效应蛋白AnkX.
- AnkX使用CDP-胆调解Rab1和Rab35的胆化,需要其FIC域.
结论:
- 通过细菌FIC域蛋白质的化化是一种改变宿主细胞功能的机制.
- AnkX对Rab GTPases的基化作用影响了内细胞和外细胞通路.
- 这项研究揭示了军团菌用来控制宿主细胞运输的新策略.
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相关概念视频
Rab Proteins
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...
Rab Cascades
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.
Small GTPases - Ras and Rho
Ras and Rho are small monomeric GTPases that act downstream of receptor tyrosine kinase (RTK) and regulate various cellular processes. These GTPases switch between active and inactive states by binding to guanine nucleotides.
Three regulatory proteins control their activity:
Three regulatory proteins control their activity:
GTPases and their Regulation
Guanine nucleotide-binding proteins (G-proteins), also known as GTPases, are a superfamily of proteins that regulate many cellular processes, such as cell signaling, vesicular transport, and the regulation of cell shape and motility. Mutation or dysfunction of these proteins can lead to disease. There are around 40,000 known G-proteins that can broadly be classified into two groups ‒ small G-proteins consisting of a single domain and large multi-domain G-proteins.
Large G-proteins, also known...
Large G-proteins, also known...
GTPases and their Regulation
Guanine nucleotide-binding proteins (G-proteins), also known as GTPases, are a superfamily of proteins that regulate many cellular processes, such as cell signaling, vesicular transport, and the regulation of cell shape and motility. Mutation or dysfunction of these proteins can lead to disease. There are around 40,000 known G-proteins that can broadly be classified into two groups ‒ small G-proteins consisting of a single domain and large multi-domain G-proteins.
Large G-proteins, also known...
Large G-proteins, also known...
IP3/DAG Signaling Pathway
Membrane lipids such as phosphatidylinositol (PI) are precursors for several membrane-bound and soluble second messengers. Specific kinases phosphorylate PI and produce phosphorylated inositol phospholipids. One such inositol phospholipids are the phosphatidylinositol-4,5 bisphosphate [PI(4,5)P2], present in the inner half of the lipid bilayer. Upon ligand binding, GPCR stimulates Gq proteins to turn on phospholipase Cꞵ. Activated phospholipase Cꞵ cleaves PI(4,5)P2 and produces two-second...
