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関連する概念動画

Enzyme-linked Receptors01:00

Enzyme-linked Receptors

Enzyme-linked receptors are proteins that act as both receptor and enzyme, activating multiple intracellular signals. This is a large group of receptors that include the receptor tyrosine kinase (RTK) family. Many growth factors and hormones bind to and activate the RTKs.
Neurotrophin (NT) receptors are a family of RTKs, including trkA, trkB, and trkC (tropomyosin-related kinase) receptors. TrkA is specific for nerve growth factor (NGF), neurotrophin-6, and neurotrophin-7. TrkB binds...
Ligand Binding Sites02:40

Ligand Binding Sites

Proteins are dynamic macromolecules that carry out a wide variety of essential processes; however, the activities of most proteins depend on their interactions with other molecules or ions, known as ligands.
Protein-ligand interactions are quite specific; even though numerous potential ligands surround a cellular protein at any given time, only a particular ligand can bind to that protein. Moreover, a ligand binds only to a dedicated area on the surface of the protein, known as the...
Mitogens and the Cell Cycle02:38

Mitogens and the Cell Cycle

Mitogens and their receptors play a crucial role in controlling the progression of the cell cycle. However, the loss of mitogenic control over cell division leads to tumor formation. Therefore, mitogens and mitogen receptors play an important role in cancer research. For instance, the epidermal growth factor (EGF) - a type of mitogen and its transmembrane receptor (EGFR), decides the fate of the cell's proliferation. When EGF binds to EGFR, a member of the ErbB family of tyrosine kinase...
Receptor Downregulation in MVBs01:15

Receptor Downregulation in MVBs

Multivesicular bodies (MVBs) are mature endosomes that sort ubiquitinated proteins and then fuse with lysosomes to degrade the sorted proteins. Epidermal growth factor (EGF) and its receptor (EGFR) form a complex that can be internalized through endocytosis, sorted into an MVB, and later degraded.
The EGFR can initiate signaling pathways that  lead to cell proliferation, migration, and differentiation. Overexpression of EGFR  stimulates cells to proliferate. Excessive  EGFR activation may...
GPCR Desensitization01:12

GPCR Desensitization

G protein-coupled receptor (GPCR) signaling plays a crucial role in cell functioning. GPCR desensitization is an equally essential process. It allows cells to respond to changing environments and regain sensitivity to new stimuli while preventing unnecessary stimulation when no longer needed. Prolonged exposure to stimuli leads to GPCR desensitization. It involves blocking the receptors from binding and activating additional G proteins. This inhibits activation of downstream effectors, thereby...
GPCRs Regulate Adenylyl Cylase Activity01:09

GPCRs Regulate Adenylyl Cylase Activity

Some GPCRs transmit signals through adenylyl cyclase (AC), a transmembrane enzyme. AC helps synthesize second messenger cyclic adenosine monophosphate (cAMP). AC catalyzes cyclization reaction and converts ATP to cAMP by releasing a pyrophosphate. The pyrophosphate is further hydrolyzed to phosphate by the enzyme pyrophosphatase, which drives cAMP synthesis to completion. However, cAMP is rapidly degraded to 5′ AMP by the enzymes phosphodiesterase (PDE), preventing overstimulation of cells.
Two...

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関連する実験動画

Updated: Jun 11, 2026

Studying the Stoichiometry of Epidermal Growth Factor Receptor in Intact Cells using Correlative Microscopy
09:16

Studying the Stoichiometry of Epidermal Growth Factor Receptor in Intact Cells using Correlative Microscopy

Published on: September 11, 2015

アルゴスによるEGFRリガンド結合の構造的基礎

Daryl E Klein1, Steven E Stayrook, Fumin Shi

  • 1Department of Biochemistry and Biophysics, University of Pennsylvania School of Medicine, 809C Stellar-Chance Laboratories, 422 Curie Boulevard, Philadelphia, Pennsylvania 19104-6059, USA.

Nature
|May 27, 2008
PubMed
まとめ

アルゴス (Argos) はドロソフィラのタンパク質で,表皮成長因子 (EGF) のリガンドを結合させ,表皮成長因子受容体 (EGFR) のシグナル伝達を阻害する. EGFRとは無関係な,クランプのような独特な構造は,抗がん療法薬の設計に潜在的可能性を秘めている.

科学分野:

  • 構造生物学 構造生物学とは
  • 分子生物学と細胞生物学について
  • バイオケミストリー バイオケミストリー

背景:

  • 皮膚表皮成長因子受容体 (EGFR) のシグナル伝達は発達に不可欠ですが,癌には関与しています.
  • ドロソフィラのタンパク質であるArgosは,EGFRのリガンドを結合することによってEGFRシグナル伝達を阻害する.
  • アルゴスの構造を理解することは,抗がん剤の開発の鍵です.

研究 の 目的:

  • EGFRリガンドに結合したアルゴスの結晶構造を決定する.
  • アルゴス媒介によるEGFRリガンド結合の分子メカニズムを解明する.
  • アルゴスとその構造的同類体の潜在的な治療用途を探求する.

主な方法:

  • 1.6-A解像度でのX線結晶学.
  • 構造分析と既知のタンパク質ファミリーとの比較.
  • 潜在的哺乳類同類を特定するためのバイオインフォマティクス.

主要な成果:

  • 結晶構造は,ArgosがEGFのようなドメインではなく,3つのドメイン,クランプのような折りたたみを持っていることを示しています.
  • アルゴスはEGFのリガンドを二重の表面で結合させ,EGFRの機能を模倣する.

さらに関連する動画

Deciphering the Structural Effects of Activating EGFR Somatic Mutations with Molecular Dynamics Simulation
15:05

Deciphering the Structural Effects of Activating EGFR Somatic Mutations with Molecular Dynamics Simulation

Published on: May 20, 2020

Modeling Ligands into Maps Derived from Electron Cryomicroscopy
09:30

Modeling Ligands into Maps Derived from Electron Cryomicroscopy

Published on: July 19, 2024

関連する実験動画

Last Updated: Jun 11, 2026

Studying the Stoichiometry of Epidermal Growth Factor Receptor in Intact Cells using Correlative Microscopy
09:16

Studying the Stoichiometry of Epidermal Growth Factor Receptor in Intact Cells using Correlative Microscopy

Published on: September 11, 2015

Deciphering the Structural Effects of Activating EGFR Somatic Mutations with Molecular Dynamics Simulation
15:05

Deciphering the Structural Effects of Activating EGFR Somatic Mutations with Molecular Dynamics Simulation

Published on: May 20, 2020

Modeling Ligands into Maps Derived from Electron Cryomicroscopy
09:30

Modeling Ligands into Maps Derived from Electron Cryomicroscopy

Published on: July 19, 2024

  • アルゴスドメインは,TGF-β受容体とuPA受容体と構造的に類似しています.
  • 結論:

    • Argosは,EGFRリガンドを隔離するために新しい構造的メカニズムを使用しています.
    • 哺乳類のArgos同種が存在し,さらなる調査を正当化する可能性がある.
    • この構造は,人工EGF隔離抗癌薬の設計のための青写真を提供します.