通过细菌的催化脚手架组装一个GTPase-kinase信号复合体
Andrey S Selyunin1, Sarah E Sutton, Bethany A Weigele
1Department of Microbiology, University of Texas Southwestern Medical Center, 5323 Harry Hines Boulevard, Dallas, Texas 75390-8816, USA.
Nature
|December 21, 2010
概括
肠道出血性大肠杆菌效应物 EspG 作为催化支架,通过组织 GTPase 和激酶复合体来重新编程宿主细胞信号. 这种细菌蛋白质抑制了GTPase信号传递,并激活了激酶通路.
科学领域:
- 微生物学 微生物学
- 细胞生物学 细胞生物学
- 结构生物学 结构生物学
背景情况:
- 脚手架蛋白质通过将酶组装成信号电路来调节细胞信息流.
- 细菌效应蛋白可以通过翻译后修改来抑制这些电路.
- 病原体可能使用酶架直接组织宿主信号网络,但效应者和机制通常是未知的.
研究的目的:
- 确定组织高阶信号网络的细菌效应器.
- 阐明这些效应器操纵宿主细胞信号的机制.
- 描述效应器功能的结构基础.
主要方法:
- 功能查以确定调节内膜贩运的效应蛋白.
- 结晶学用于确定效应体-宿主蛋白质复合物的结构.
- 生物化学试验分析酶活性和抑制.
主要成果:
- 来自肠道出血性大肠杆菌O157:H7的III类效应体EspG被确定为内膜贩运的调节者.
- EspG的点是ADP-ribosylation因子 (ARF) GTPases和p21激活酶 (PAKs). EspG的点是ADP-ribosylation因子 (ARF) GTPases和p21激活酶 (PAKs). EspG的点是ADP-ribosylation因子 (ARF) GTPases和p21激活酶 (PAKs). EspG的点是ADP-ribosylation因子 (ARF) GTPases和p21激活酶 (PAKs).
- 结构研究显示,EspG抑制了ARF的GTPase活性,并以性方式激活了PAK激酶活性,作为GTPase-激酶信号复合体的催化支架.
结论:
- EspG作为一种新的"催化支架"功能,同时调节GTPase和激酶信号通路.
- 这种由EspG对宿主细胞信号的重编程为细菌病原发生提供了一个新的机制.
- 了解这些效应器功能,可以了解细胞信号网络的调节.
相关概念视频
Assembly of Signaling Complexes
Multiprotein signaling complexes are formed in a dynamic process involving protein-protein interactions at the cytoplasmic domain of transmembrane receptors or enzymatic and non-enzymatic proteins associated with the receptor. These complexes ensure the activation and propagation of intracellular signals that regulate cell functions.
Interaction domains in cell signaling
Interaction domains recognize exposed features of their binding partners containing post-translationally modified sequences,...
Interaction domains in cell signaling
Interaction domains recognize exposed features of their binding partners containing post-translationally modified sequences,...
Coat Assembly and GTPases
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...
Amplifying Signals via Enzymatic Cascade
When a ligand binds to a cell-surface receptor, the receptor's intracellular domain changes shape, which may either activate its enzyme function or allow its binding to other molecules. The initial signal is amplified by most signal transduction pathways. This means that a single ligand molecule can activate multiple molecules of a downstream target. Proteins that relay a signal are most commonly phosphorylated at one or more sites, activating or inactivating the protein. Kinases catalyze the...
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.
Protein Complex Assembly
Proteins can form homomeric complexes with another unit of the same protein or heteromeric complexes with different types. Most protein complexes self-assemble spontaneously via ordered pathways, while some proteins need assembly factors that guide their proper assembly. Despite the crowded intracellular environment, proteins usually interact with their correct partners and form functional complexes.
Many viruses self-assemble into a fully functional unit using the infected host cell to...
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Protein Complex Assembly
Proteins can form homomeric complexes with another unit of the same protein or heteromeric complexes with different types. Most protein complexes self-assemble spontaneously via ordered pathways, while some proteins need assembly factors that guide their proper assembly. Despite the crowded intracellular environment, proteins usually interact with their correct partners and form functional complexes.
Many viruses self-assemble into a fully functional unit using the infected host cell to...
Many viruses self-assemble into a fully functional unit using the infected host cell to...


