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相关概念视频

ER Retrieval Pathway01:45

ER Retrieval Pathway

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In the secretory pathway, vesicles transport proteins from one cellular compartment to another in forward transport to deliver the protein to its correct location. Occasionally, misfolded proteins and incorrect proteins escape their original compartments, and a retrieval pathway is used to return the escaped proteins to their original compartment.
The ER uses many checkpoints to prevent the entry of incorrectly folded or a resident protein as cargo onto a transport vesicle. These mechanisms...
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SNAREs and Membrane Fusion01:43

SNAREs and Membrane Fusion

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Once a transport vesicle has recognized its target organelle, the vesicular membrane needs to fuse with the target membrane to unload the cargo. Transmembrane proteins called SNAREs present on organelle membranes and their vesicles, mediate vesicle fusion.
SNAREs exist in pairs that symmetrically interact and catalyze the fusion of the lipid bilayers in vesicle and target organelle. v-SNARE in the vesicle membrane are single polypeptide chains that bind to a complementary t-SNARE, composed of 2...
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The Early Endosome: Endocytosis of Transferrin01:28

The Early Endosome: Endocytosis of Transferrin

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Essential proteins such as insulin or low-density lipoprotein (LDL) and micronutrients such as iron enter a eukaryotic cell through receptor-mediated endocytosis. Subsequently, the early endosomes fuse with the vesicles containing such receptor-ligand complexes and play a vital role in sorting the incoming ligands and receptors. While the ligands are either degraded inside the vesicle or released into the cytosol, their receptors are returned to the plasma membrane for further rounds of...
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Tail-anchoring of Proteins in the ER Membrane01:45

Tail-anchoring of Proteins in the ER Membrane

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Tail-anchored, or TA, proteins are estimated to make up to 3-5% of membrane proteins found in the eukaryotic cell. Such proteins have a single transmembrane domain located approximately 30 amino acid residues upstream from the C-terminal end. As a result, the signal recognition particle (SRP) cannot guide a TA protein to the ER membrane for cotranslational insertion. Hence, they are integrated into the ER membrane post-translationally using their C-terminal end as the anchor. TA proteins...
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Clathrin Coated Vesicles01:12

Clathrin Coated Vesicles

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Clathrin-coated vesicles use endocytosis to transport receptors and lysosomal hydrolases from the Golgi to the lysosome in the late secretory pathway. Clathrin-mediated endocytosis was the first described endocytic process, and Clathrin-coated vesicles remain one of the most well-studied transport vesicles. The molecular machinery that generates clathrin-coated vesicles comprises over 50 proteins that precisely coordinate vesicle formation. Cell surface receptors concentrated in indented sites...
6.8K
Nuclear Protein Sorting01:34

Nuclear Protein Sorting

4.5K
Nuclear protein sorting is the selective trafficking of histones, polymerases, gene regulatory proteins into the nucleus and exporting RNAs and ribosomes to the cytosol. It is a tightly controlled process that regulates gene expression within a cell.
Proteins targeted to the nucleus carry nuclear localization signals or NLS recognized by import receptors in the cytosol. Similarly, proteins with nuclear export signals are recognized by export receptors. Import and export receptors are...
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相关实验视频

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Expression, Purification, and Liposome Binding of Budding Yeast SNX-BAR Heterodimers
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恢复者-SNX17组装和内体组分的结构基础.

Amika Singla1, Daniel J Boesch2, Ho Yee Joyce Fung3

  • 1Department of Internal Medicine, University of Texas Southwestern Medical Center, 5323 Harry Hines Boulevard, Dallas, TX, 75390, USA.

Nature communications
|November 25, 2024
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概括

排序Nexin 17 (SNX17) 将货物连接到回收复合体进行内体循环. 货物绑定释放SNX17的释放

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科学领域:

  • 细胞生物学 细胞生物学
  • 分子生物学分子生物学
  • 结构生物学 结构生物学

背景情况:

  • 排序Nexin 17 (SNX17) 对于内体循环至关重要,它通过与Retriever复合体相互作用来调解载荷蛋白质的运输.
  • 控制SNX17-Retriever相互作用的精确分子机制尚未完全阐明.

研究的目的:

  • 阐明Sorting Nexin 17 (SNX17) -Retriever复杂相互作用的结构和生化机制.
  • 了解货物结合如何调节SNX17与Retriever的相互作用以及随后的内体体贩运.

主要方法:

  • 生物化学测定 生物化学测定
  • 低温电子显微镜 (cryo-EM) 是一种电子显微镜.
  • 蛋白质组学是指蛋白质组学.
  • 细胞成像 细胞成像

主要成果:

  • SNX17存在于自抑制状态,其FERM域与其C端尾结合.
  • 货物绑定到SNX17的FERM域释放C终端尾部,然后绑定到Retriever的VPS35L/VPS26C接口.
  • 这种接口的破坏会损害货物回收,并改变血膜蛋白质组合.
  • 猎犬的结合口袋容纳了具有酸性C端纹理的其他配体.

结论:

  • 揭示了SNX17介导的内体载荷循环的新机制,涉及载荷诱导的SNX17C端尾部释放以绑定Retriever.
  • 这些发现提供了对SNX17-Retriever相互作用及其由货物调节的结构性见解.
  • 这项研究突出了Retriever与多种连接体相互作用的潜力,影响细胞贩运和潜在的病原体相互作用.