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相关概念视频

G Protein-coupled Receptors01:15

G Protein-coupled Receptors

11.3K
G Protein-Coupled Receptors or GPCRs are membrane-bound receptors that transiently associate with heterotrimeric G proteins and induce an appropriate response to sensory stimuli such as light, odors, hormones, cytokines, or neurotransmitters.
GPCRs are also called heptahelical, 7TM, or serpentine receptors, and consist of seven (H1-H7) transmembrane alpha-helices that span the bilayer to form a cylindrical core. The transmembrane helices are connected by three extracellular loops and three...
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G-protein Coupled Receptors01:21

G-protein Coupled Receptors

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G-protein coupled receptors are ligand binding receptors that indirectly affect changes in the cell. The actual receptor is a single polypeptide that transverses the cell membrane seven times creating intracellular and extracellular loops. The extracellular loops create a ligand specific pocket which binds to neurotransmitters or hormones. The intracellular loops holds onto the G-protein.
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Intracellular Signaling Affects Focal Adhesions01:17

Intracellular Signaling Affects Focal Adhesions

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Integrins act both as extracellular input receivers and as intracellular processing activators. As their name suggests, integrins are entirely integrated into the membrane structure. Their hydrophobic membrane-spanning regions interact with the phospholipid bilayer's hydrophobic region. These membrane receptors provide extracellular attachment sites for effectors like hormones and growth factors. They activate intracellular response cascades when their effectors are bound and active.
Some...
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Assembly of Signaling Complexes01:30

Assembly of Signaling Complexes

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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,...
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Transducer Mechanism: G Protein–Coupled Receptors01:30

Transducer Mechanism: G Protein–Coupled Receptors

1.8K
G Protein–Coupled Receptors (GPCRs) are membrane-bound receptors that transiently associate with heterotrimeric G proteins and induce an appropriate response to various stimuli. GPCRs regulate critical physiological pathways and are excellent drug targets for treating diseases such as diabetes, cancer, obesity, depression, or Alzheimer's. Nearly 35% of approved drugs implement their therapeutic effects by selectively interacting with specific GPCRs.
GPCRs are also called heptahelical,...
1.8K
GPCRs Regulate Adenylyl Cylase Activity01:09

GPCRs Regulate Adenylyl Cylase Activity

5.3K
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...
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相关实验视频

Updated: Jun 5, 2025

Visualizing the Conformational Dynamics of Membrane Receptors Using Single-Molecule FRET
10:59

Visualizing the Conformational Dynamics of Membrane Receptors Using Single-Molecule FRET

Published on: August 17, 2022

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细胞外和膜外域之间的 conformational 合调节全粘附 GPCR 功能.

Szymon P Kordon1,2,3,4, Kristina Cechova5, Sumit J Bandekar1,2,3,4

  • 1Department of Biochemistry and Molecular Biology, The University of Chicago, Chicago, IL, USA.

Nature communications
|December 3, 2024
PubMed
概括
此摘要是机器生成的。

粘附G蛋白结合受体 (aGPCRs) 使用其细胞外区域进行信号传递. 这项研究揭示了GAIN域如何增长.

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Transmembrane Domain Oligomerization Propensity determined by ToxR Assay
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Transmembrane Domain Oligomerization Propensity determined by ToxR Assay

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G Protein-selective GPCR Conformations Measured Using FRET Sensors in a Live Cell Suspension Fluorometer Assay
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相关实验视频

Last Updated: Jun 5, 2025

Visualizing the Conformational Dynamics of Membrane Receptors Using Single-Molecule FRET
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Visualizing the Conformational Dynamics of Membrane Receptors Using Single-Molecule FRET

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Transmembrane Domain Oligomerization Propensity determined by ToxR Assay
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Transmembrane Domain Oligomerization Propensity determined by ToxR Assay

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G Protein-selective GPCR Conformations Measured Using FRET Sensors in a Live Cell Suspension Fluorometer Assay
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G Protein-selective GPCR Conformations Measured Using FRET Sensors in a Live Cell Suspension Fluorometer Assay

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科学领域:

  • 结构生物学是结构生物学.
  • 蜂信号传输是如何进行的
  • 生物化学 生物化学

背景情况:

  • 粘附G蛋白结合受体 (aGPCRs) 是重要的细胞粘附分子,调节各种生理过程.
  • aGPCRs具有大型的细胞外区域 (ECRs),其保存的GAIN域在它们的七通跨膜 (7TM) 域之前.
  • 对于ECR影响7TM活动的机制,特别是ECR与7TM相比的方向和动态,人们对其理解程度仍然不佳.

研究的目的:

  • 在aGPCR中阐明ECR和7TM之间的结构和动态关系.
  • 研究GAIN域的方向和运动如何影响GPCR功能.
  • 探索GAIN-7TM接口变化的功能后果.

主要方法:

  • 电子显微镜 (cryo-EM) 用于拉特罗菲林3/ADGRL3.3的高分辨率结构重建.
  • 单分子弗斯特共振能量转移 (smFRET) 探测ECR-7TM动态.
  • 功能性测试评估受体信号响应GAIN向抗体和突变的反应.

主要成果:

  • 冷-EM结构显示了GAIN域相对于移动性受限的7TM区域的平行方向.
  • smFRET实验确定了ECR相对于7TM的三个不同的,缓慢相互转换的形状状态.
  • 针对GAIN域或GAIN-7TM接口的修改改变了这些构造状态,冷-EM结构和受体信号活动.

结论:

  • 在aGPCR中显示了ECR和7TM之间的直接形状和功能合.
  • 表明ECR,特别是GAIN域,调解aGPCR激活的机制.
  • 强调GAIN-7TM接口在调节aGPCR信号通路方面的重要性.