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相关概念视频

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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相关实验视频

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

通过阿戈斯对EGFR连接的结构基础.

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
概括

阿戈斯是一种多索菲拉蛋白,结合了表皮生长因子 (EGF) 连接体,以抑制表皮生长因子受体 (EGFR) 信号传递. 它独特的状结构与EGFR无关,为设计抗癌疗法提供了潜力.

科学领域:

  • 结构生物学是结构生物学.
  • 分子和细胞生物学分子和细胞生物学.
  • 生物化学 生物化学

背景情况:

  • 皮表皮生长因子受体 (EGFR) 信号传递对发育至关重要,但与癌症有关.
  • 阿戈斯是一种多索菲拉菌的蛋白质,通过结合其连接物来抑制EGFR信号传递.
  • 了解Argos的结构是开发抗癌剂的关键.

研究的目的:

  • 为了确定阿戈斯结合EGFR连接体的晶体结构.
  • 为了阐明阿尔戈斯介导的EGFR配体结合的分子机制.
  • 探索Argos及其结构同类的潜在治疗应用.

主要方法:

  • 在1.6A分辨率的X射线晶体学.
  • 结构分析和与已知的蛋白质家族进行比较.
  • 生物信息学用于识别潜在的哺乳动物同类物.

主要成果:

  • 晶体结构显示Argos具有三个域,类似紧的折叠,而不是类似EGF的域.
  • 阿戈斯通过双部分表面结合了EGF连接体,模仿了EGFR的功能.
  • 阿戈斯域与TGF-β受体和uPA受体具有结构上的相似之处.

更多相关视频

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

相关实验视频

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

结论:

  • 阿戈斯利用了一种新的结构机制来隔离EGFR配体.
  • 哺乳动物Argos的同类可能存在,需要进一步调查.
  • 该结构为设计人工EGF隔离抗癌药物提供了蓝图.