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Updated: Jun 5, 2026

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Comparing the Affinity of GTPase-binding Proteins using Competition Assays
Published on: October 8, 2015
GTPase-キナーゼシグナル伝達複合体の組み立ては,バクテリアの触媒的支架によって行われます
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
まとめ
エントロヘモラジックE. coliエフェクタ EspGは触媒的支架として作用し,GTPaseとキナーゼ複合体を組織することによって宿主細胞のシグナル伝達を再プログラムします. この細菌のタンパク質は,GTPaseシグナル伝達を阻害し,キナーゼ経路を活性化します.
科学分野:
- 微生物学 微生物学とは
- 細胞生物学 細胞生物学
- 構造生物学 構造生物学とは
背景:
- 骨組みのタンパク質は,信号回路に酵素を組み込むことで,細胞の情報流れを調節する.
- バクテリアのエフェクタータンパク質は,翻訳後の修正によってこれらの回路を阻害することができます.
- 病原体は,酵素構造を用いて宿主シグナル伝達ネットワークを直接組織するかもしれないが,効果因子やメカニズムはしばしば不明である.
研究 の 目的:
- 高級信号ネットワークを組織する細菌エフェクターを特定する.
- これらのエフェクターが宿主細胞の信号伝達を操作するメカニズムを解明する.
- エフェクタ機能の構造的基礎を特徴づける.
主な方法:
- 内膜の密輸を調節するエフェクタータンパク質を特定するための機能スクリーニング.
- 効果体-宿主タンパク質複合体の構造を決定するための結晶学.
- 酵素活性と阻害を分析するための生化学分析.
主要な成果:
- 腸出血性Escherichia coli O157:H7からのタイプIIIエフェクターEspGは,内膜密輸の調節剤として特定されました.
- EspGはADP-リボシライゼーションファクター (ARF) GTPasesとp21活性化キナーゼ (PAKs) を標的にする.
- 構造的研究により,EspGはARFのGTPase活性を抑制し,PAKキナーゼ活性をアロステリックに活性化させ,GTPase-キナーゼシグナル伝達複合体の触媒的支架として作用することを明らかにした.
結論:
- EspGは,新しい"触媒的支架"として機能し,同時にGTPaseとキナーゼの信号伝達経路を調節します.
- EspGによる宿主細胞のシグナル伝達のこの再プログラミングは,細菌の病原化のための新しいメカニズムを提供します.
- これらのエフェクター機能を理解することで,セルラー信号ネットワークの調節に関する洞察が得られます.
関連する概念動画
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...
Many viruses self-assemble into a fully functional unit using the infected host cell to...
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...

