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関連する概念動画

Amplifying Signals via Enzymatic Cascade01:22

Amplifying Signals via Enzymatic Cascade

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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...
15.3K
Amplifying Signals via Second Messengers01:15

Amplifying Signals via Second Messengers

6.1K
Many receptor binding ligands are hydrophilic; they do not cross the cell membrane but bind to cell-surface receptors. Thus, their message must be relayed by second messengers present in the cell cytoplasm. There are several second messenger pathways, each with its own way of relaying information. For example, the G protein-coupled receptors can activate both phosphoinositol and cyclic AMP (cAMP) second messenger pathways. The phosphoinositol pathway is active when the receptor induces...
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IP3/DAG Signaling Pathway01:11

IP3/DAG Signaling Pathway

12.5K
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...
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Transducer Mechanism: Enzyme-Linked Receptors01:27

Transducer Mechanism: Enzyme-Linked Receptors

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Enzyme-linked receptors are cell-surface receptors acting as an enzyme or associating with an enzyme intracellularly. They make excellent drug targets. Drugs can bind to the extracellular ligand-binding domain or directly affect their enzymatic domain and alter their activity.
Major types that are helpful drug targets include:
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Intracellular Signaling Cascades01:24

Intracellular Signaling Cascades

44.8K
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...
44.8K
Interactions Between Signaling Pathways01:19

Interactions Between Signaling Pathways

4.7K
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...
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Characterization at the Molecular Level using Robust Biochemical Approaches of a New Kinase Protein
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Characterization at the Molecular Level using Robust Biochemical Approaches of a New Kinase Protein

Published on: June 30, 2019

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リガンドゲートスプリットキナーゼ

Karla Camacho-Soto1, Javier Castillo-Montoya, Blake Tye

  • 1Department of Chemistry and Biochemistry, University of Arizona , 1306 East University Boulevard, Tucson, Arizona 85721, United States.

Journal of the American Chemical Society
|February 19, 2014
PubMed
まとめ
この要約は機械生成です。

研究者は,ユーザー定義の入力によって制御されるよう,タンパク質キナーゼを設計した. この方法は,不活性な断片から,リガンドゲートされた分裂タンパク質キナーゼを生成し,分子生物学における新しい応用を可能にします.

さらに関連する動画

Use of Label-free Optical Biosensors to Detect Modulation of Potassium Channels by G-protein Coupled Receptors
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Use of Label-free Optical Biosensors to Detect Modulation of Potassium Channels by G-protein Coupled Receptors

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Spatiotemporal Control of Protein Activity through Optogenetic Allosteric Regulation
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Spatiotemporal Control of Protein Activity through Optogenetic Allosteric Regulation

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Characterization at the Molecular Level using Robust Biochemical Approaches of a New Kinase Protein
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Use of Label-free Optical Biosensors to Detect Modulation of Potassium Channels by G-protein Coupled Receptors
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Spatiotemporal Control of Protein Activity through Optogenetic Allosteric Regulation
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Spatiotemporal Control of Protein Activity through Optogenetic Allosteric Regulation

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科学分野:

  • バイオケミストリー バイオケミストリー
  • 分子生物学は分子生物学である.
  • プロテイン工学は,タンパク質の

背景:

  • タンパク質キナーゼの活動は,リン酸化や金属イオンなどの自然な生理化学的入力によって調節されます.
  • ユーザ定義制御による合成タンパク質キナーゼの設計は,バイオテクノロジーの重要な課題です.

研究 の 目的:

  • ユーザ定義の入力に反応するタンパク質キナーゼを設計する方法を開発する.
  • 触媒活性を維持した新しいリガンドゲート分裂タンパク質キナーゼを作成する.

主な方法:

  • 配列不類似性アプローチを用いて,タンパク質キナーゼにおける25-残基ループ挿入に適した場所を特定した.
  • 成功したループ挿入変異体は,キナーゼを不活性な断片に解剖することを導いた.
  • 断片の再組み立ては,リガンド結合によって誘発され,活性分裂タンパク質キナーゼを生成しました.

主要な成果:

  • タンパク質キナーゼの特定の部位を特定し,触媒機能を維持しながらループ挿入を許容する.
  • Lyn,Fak,Src,PKAを用いたリガンドゲート分裂タンパク質キナーゼの成功エンジニアリングを実証した.
  • 異なるキナーゼファミリーにおける開発されたアプローチの潜在的汎用性を示した.

結論:

  • 配列不類似性ベースの方法は,制御可能なタンパク質キナーゼの設計に有効です.
  • このアプローチにより,特定のリガンドに反応する,触媒的に活性な分裂タンパク質キナーゼの生成が可能になります.
  • この発見は,カスタムゲートキナーゼのエンジニアリングの広範な適用可能性を示唆しています.