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相关概念视频

G-Protein Gated Ion Channels01:21

G-Protein Gated Ion Channels

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GPCRs are primarily responsible for our sense of smell, taste, and vision.  The binding of a sensory stimulus activates GPCR to stimulate effector proteins, many of which are ion channels in the sensory organs. GPCRs modulate the opening and closing of the target ion channels either directly by binding them, or by releasing second messengers that activate these channels. As ions move across the membrane, the membrane potential is altered, which induces an appropriate response.
Sensory...
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Transducer Mechanism: G Protein–Coupled Receptors01:30

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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,...
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G-protein Coupled Receptors01:21

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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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Gastrulation01:56

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Gastrulation establishes the three primary tissues of an embryo: the ectoderm, mesoderm, and endoderm. This developmental process relies on a series of intricate cellular movements, which in humans transforms a flat, “bilaminar disc” composed of two cell sheets into a three-tiered structure. In the resulting embryo, the endoderm serves as the bottom layer, and stacked directly above it is the intermediate mesoderm, and then the uppermost ectoderm. Respectively, these tissue strata...
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GTPases and their Regulation02:14

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Guanine nucleotide-binding proteins (G-proteins), also known as GTPases, are a superfamily of proteins that regulate many cellular processes, such as cell signaling, vesicular transport, and the regulation of cell shape and motility. Mutation or dysfunction of these proteins can lead to disease. There are around 40,000 known G-proteins that can broadly be classified into two groups ‒  small G-proteins consisting of a single domain and large multi-domain G-proteins.
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One of the challenges of using the second law of thermodynamics to determine if a process is spontaneous is that it requires measurements of the entropy change for the system and the entropy change for the surroundings. An alternative approach involving a new thermodynamic property defined in terms of system properties only was introduced in the late nineteenth century by American mathematician Josiah Willard Gibbs. This new property is called the Gibbs free energy (G) (or simply the free...
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GzESTY作为一个优化的基于细胞的试验,用于GPCR脱化的初步步骤.

Luca Franchini1, Joseph J Porter1, John D Lueck1

  • 1Department of Pharmacology and Physiology, University of Rochester Medical Center, Rochester, NY, 14642, USA.

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概括

一种新的测定,GzESTY,有助于发现G蛋白结合受体 (GPCRs) 的配体,特别是孤儿GPCRs. 该工具有助于识别未知的药物点,并了解GPCR功能.

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科学领域:

  • 药理学 药理学是指药理学的学科.
  • 分子生物学分子生物学
  • 测试开发 测试开发

背景情况:

  • G蛋白结合受体 (GPCRs) 是关键的药物标,但许多,特别是孤儿GPCRs,由于未知的配体和激活机制而未得到充分利用.
  • 大多数GPCR通过G$_{i/o/z}$家族发出信号,但目前的激活试验有限,阻碍了连接体的发现.

研究的目的:

  • 介绍GzESTY,一种新的,敏感的基于细胞的试验,用于研究G$_{i/o/z}$-合的GPCR药理学.
  • 通过启用配体鉴定,促进孤儿GPCRs的脱化.

主要方法:

  • 开发和优化GzESTY试验,使用一个全集向量来实现精确的组件表达.
  • 选配体激活GPCRs和内源GPCRs的库,以评估测试性能.

主要成果:

  • GzESTY成功检测了各种GPCRs的激活,区分了完全和部分激动.
  • 该试验在脑部提取物中确定了GPR176和GPR37的内源配体,证明了其脱效用.

结论:

  • GzESTY是用于GPCR药理学研究和连接体发现的敏感和多功能工具.
  • 这种测试扩大了识别孤儿GPCRs配体的能力,推进了药物标探索.