2つのコンポーネントの信号伝達システムの特異性を再配線する
Jeffrey M Skerker1, Barrett S Perchuk, Albert Siryaporn
1Department of Biology, Massachusetts Institute of Technology, Cambridge, MA 02139, USA.
Cell
|June 17, 2008
まとめ
バクテリアは,環境を感知するために2つのコンポーネントのシグナリングシステムを使用します. アミノ酸の共進化を分析した結果,突然変異するとヒスティジンキナーゼの特異性を切り替え,経路の再配線を可能にする重要な残留物が明らかになった.
科学分野:
- 微生物学 微生物学とは
- 分子生物学は分子生物学である.
- バイオケミストリー バイオケミストリー
背景:
- 2つのコンポーネントの信号伝達システム (TCS) は,細菌の環境感知と反応に不可欠です.
- ヒスティジンキナーゼ (HKs) と応答調節体 (RRs) で構成されるこれらのシステムは,信号の交響を防ぐために特定の相互作用を必要とします.
- バクテリアは多数の並列のTCSを利用し,HK-RRの正確な認識のためのメカニズムを必要とします.
研究 の 目的:
- 細菌の2つの成分信号伝達経路における特異性を支配する分子決定因子を特定する.
- HK-RR相互作用特異性を決定するアミノ酸共進化の役割を調査する.
- 標的型変異によってTCS特異性を合理的に変化させる可能性を実証する.
主な方法:
- アミノ酸共進化のパターンを検出するために,同類のHK-RRペアの大規模,複数の配列の配列の分析.
- EnvZヒスティジンキナーゼ内の同進化する残基の特定されたサイト指向型変異.
- EnvZ基板特異性とHK-RR相互作用に対する突然変異の影響を評価する.
主要な成果:
- HK-RRペア内のアミノ酸共進化の特定のパターンを特定し,信号特異性と相関しています.
- EnvZにおける共進化する残留物のサブセットを突然変異させることが,その基質特異性を完全に変化させるのに十分であることを実証した.
- 標的型遺伝子改変によってEnvZキナーゼの標的を切り替える能力を示した.
結論:
- アミノ酸共進化分析は,タンパク質-タンパク質相互作用特異性の決定因子を明らかにするための強力なツールです.
- 特定された共進化する残留物は,2つの構成要素のシグナル伝達における分子差別に極めて重要です.
- この研究は,細菌のシグナル伝達経路と潜在的に他のタンパク質-タンパク質相互作用システムを合理的に再接続するための一般化可能な方法を提供します.
さらに関連する動画
08:51Applying an Inducible Expression System to Study Interference of Bacterial Virulence Factors with Intracellular Signaling
Published on: June 25, 2015
9.7K
12:24DNA-affinity-purified Chip DAP-chip Method to Determine Gene Targets for Bacterial Two component Regulatory Systems
Published on: July 21, 2014
17.4K
関連する概念動画
01:28Global Regulatory Systems
838
Global regulatory systems in bacteria enable rapid and coordinated responses to environmental changes by integrating sensory inputs with gene expression, ensuring efficient adaptation to fluctuating conditions. Key global regulatory mechanisms include regulons, two-component systems, sigma factors, and secondary messengers.Regulons and Global RegulatorsA regulon is a collection of genes and operons controlled by a common global regulator. These regulators enable bacteria to prioritize resource...
838
01:22Amplifying Signals via Enzymatic Cascade
19.0K
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...
19.0K
01:30Assembly of Signaling Complexes
7.0K
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,...
7.0K
01:19Interactions Between Signaling Pathways
7.7K
Signaling cascades usually lack linearity. Multiple pathways interact and regulate one another, allowing cells to integrate and respond to diverse environmental stimuli.
Convergence and divergence, and cross-talk between signaling pathways
Two distinct signaling pathways can converge on a single functional unit, which may either be a single protein or a complex of proteins. The response is either functionally distinct or synergistic between the two pathways but different from the response...
Convergence and divergence, and cross-talk between signaling pathways
Two distinct signaling pathways can converge on a single functional unit, which may either be a single protein or a complex of proteins. The response is either functionally distinct or synergistic between the two pathways but different from the response...
7.7K
01:26Signal Transduction: Overview
12.3K
Cells respond to many types of information, often through receptor proteins positioned on the membrane. They respond to chemical signals, such as hormones, neurotransmitters, and other signaling molecules, initiating a series of molecular reactions to produce an appropriate response. This is called signal transduction. Cells also coordinate different responses elicited by the same signaling molecule via mediators, allowing molecular cross-talk.
Typically, signal transduction involves three...
Typically, signal transduction involves three...
12.3K
01:24Intracellular Signaling Cascades
54.8K
Once a ligand binds to a receptor, the signal is transmitted through the membrane and into the cytoplasm. The continuation of a signal in this manner is called signal transduction. Signal transduction only occurs with cell-surface receptors, which cannot interact with most components of the cell, such as DNA. Only internal receptors can interact directly with DNA in the nucleus to initiate protein synthesis. When a ligand binds to its receptor, conformational changes occur that affect the...
54.8K