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相关概念视频

Structure of Cadherins01:25

Structure of Cadherins

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The cadherins were one of the first cell adhesion molecules discovered; the term “cadherins”   is based on their calcium-dependent adhering properties. The first cadherins discovered on the epithelial, neuronal, and placental cells were named E-cadherin, P-cadherin, and N-cadherin, respectively. These classical cadherins share sequence and structural similarities. Other cadherins, including those involved in cell signaling, are grouped into non-classical cadherins. This...
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Multi-pass Transmembrane Proteins and β-barrels01:09

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In multi-pass transmembrane proteins, the polypeptide chain crosses the membrane more than once. The transmembrane polypeptide chain either forms an α-helix or β-strand structure. α-Helix containing multi-pass transmembrane proteins are ubiquitous, whereas β-strand containing ones are mainly found in gram-negative bacteria, mitochondria, and chloroplasts.
α-Helix containing multi-pass transmembrane proteins
Multi-pass transmembrane proteins such as...
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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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Activation and Inactivation of G Proteins01:22

Activation and Inactivation of G Proteins

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Heterotrimeric G proteins are guanine nucleotide-binding proteins. As the name suggests, heterotrimeric G proteins are composed of three subunits: alpha, beta, and gamma. They remain GDP-bound or GTP-bound inside the cells and switch between inactive/active states. The Gα subunit possesses the nucleotide-binding pocket that binds guanine nucleotides and switches between GDP or GTP-bound states. In contrast, the Gꞵ and Gγ subunits are always bound together with high...
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Ligand-Gated Ion Channel Receptor: Gating Mechanism01:30

Ligand-Gated Ion Channel Receptor: Gating Mechanism

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Ligand-gated ion channels are transmembrane proteins that play a vital role in intercellular communication and functions of the nervous system. They allow the influx of ions across the membrane once the neurotransmitter binds, allowing the subsequent transmission of electrical excitation across the neurons. Other ligand-gated ion channels, like the γ-aminobutyric acid (GABA) receptor, permit anions like chloride into the cells on the binding of the GABA molecule. Their entry into the cell...
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ATP Synthase: Structure01:18

ATP Synthase: Structure

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ATP synthase or ATPase is among the most conserved proteins found in bacteria, mammals, and plants. This enzyme can catalyze a forward reaction in response to the electrochemical gradient, producing ATP from ADP and inorganic phosphate. ATP synthase can also work in a reverse direction by hydrolyzing ATP and generating an electrochemical gradient. Different forms of ATP synthases have evolved special features to meet the specific demands of the cell. Based on their specific feature, ATP...
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相关实验视频

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Author Spotlight: Functional Site-Directed Fluorometry in Native Cells to Study Skeletal Muscle Excitability
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电压通路β子单元和α子单元域之间的复合物的结构.

Filip Van Petegem1, Kimberly A Clark, Franck C Chatelain

  • 1Cardiovascular Research Institute, Department of Biochemistry and Biophysics, University of California San Francisco, 513 Parnassus Avenue, Box 0130, San Francisco, California 94143, USA.

Nature
|May 14, 2004
PubMed
概括

电压通道 (Ca(V) 对细胞功能至关重要. β子单元 (Ca(V) beta通过α相互作用域 (AID) 与α子单元 (Ca(V) alpha1相互作用,影响道活性.

科学领域:

  • 分子生物学分子生物学
  • 生物物理学的生物物理.
  • 神经科学是一个神经科学.

背景情况:

  • 电压通道 (Ca(V) 对许多生理过程至关重要,包括肌肉收缩和神经递质释放.
  • 细胞内β子单元 (CaVβ) 通过与α相互作用域 (AID) 的α子单元 (CaVαα1) 结合来调节CaV道功能.
  • 之前的模型提出了β交互域 (BID) 作为主要的绑定站点,但其可访问性是可疑的.

研究的目的:

  • 为了阐明Ca(V) β-Ca(V) α1相互作用的结构基础.
  • 为了确定单独的Ca(V) beta2a和AID的复合体中的高分辨率晶体结构.
  • 了解Ca(V) β子单元如何影响Ca(V) 通道封闭机制.

主要方法:

  • 在X射线晶体学.
  • 蛋白质结构的确定蛋白质结构的确定
  • 蛋白质与蛋白质相互作用的结构分析

主要成果:

  • 确定了单独的Ca(V) beta2a和与AID复合的高分辨率晶体结构.
  • 该Ca(V) beta2a子单元通过保存的疏水裂结合AID,称为α结合口袋 (ABP),而不是之前提出的BID.
  • 这种相互作用将Ca(V) beta置于IS6段附近,这是Ca(V) 通道孔的关键组成部分,参与了无活化.

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结论:

  • 卡Vβ子单元通过ABP与卡Vαα1子单元的AID相互作用.
  • 这种相互作用为Ca(V) beta对Ca(V) 通道关的调节提供了一个结构机制,可能是通过影响IS6段运动.
  • 这些发现为分子层面的Ca (V) 通道功能调节提供了新的见解.