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相关概念视频

Protein Translocation Machinery on the ER Membrane01:28

Protein Translocation Machinery on the ER Membrane

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The translocon complex situated on the ER membrane is the main gateway for the protein secretory pathway. It facilitates the transport of nascent peptides into the ER lumen and their insertion into the ER membrane.
Sec61 protein conducting channel
In eukaryotes, the translocon complex comprises a core heterotrimeric translocator channel called the Sec61 complex. This channel includes three transmembrane proteins, Sec61α, Sec61β, and Sec61γ, and is the largest subunit of the...
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Translocation of proteins across membranes is an ancient process that occurs even in bacteria and archaebacteria. In fact, the components of the translocation machinery are still conserved between prokaryotes and eukaryotes.
Sec61 channel partners for cotranslational translocation
During cotranslational translocation, the Sec61 channel partners with the signal recognition particle (SRP), the signal recognition particle receptor (SR), and the ribosomes to transport the nascent polypeptide chain...
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Insertion of Single-pass Transmembrane Proteins in the RER01:26

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Integral membrane proteins are proteins adhered to the lipid bilayer of a cell organelle or membrane. They can be of two types: transmembrane integral proteins that span the lipid bilayer and monotopic proteins that are attached to either side of the membrane but do not pass through it.
Integral transmembrane proteins possess transmembrane and extra membrane domains. The transmembrane domains are primarily made of 20-25 hydrophobic amino acids arranged in a helical secondary confirmation. These...
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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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Ligand-gated Ion Channels01:19

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Ligand-gated ion channels are transmembrane proteins with a channel for ions to pass through and a binding site for a ligand. The channel opens only when a ligand attaches to the binding site.
Three Subfamilies of Ligand-gated Ion Channels
Ligand-gated ion channels fall into three subfamilies. The 'Cys-loop' includes the nicotinic acetylcholine receptors, γ-aminobutyric acid (GABA), glycine, and 5-hydroxytryptamine receptors. The second one is the 'Pore-loop' channels that...
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Energy to Drive Translocation01:37

Energy to Drive Translocation

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Mitochondrial protein import is powered by two distinct energy sources: ATP hydrolysis and electrochemical potential across the inner membrane. Newly synthesized precursors are bound by cytosolic chaperones of the Hsp70 family, which guide them to the import receptors on the mitochondrial surface. Utilizing the energy of ATP hydrolysis, Hsp70 chaperones transfer these precursors to the TOM receptors on the mitochondrial outer membrane.
Generally, polypeptides are unfolded by two distinct...
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相关实验视频

Updated: Feb 21, 2026

Expression and Purification of the Human Lipid-sensitive Cation Channel TRPC3 for Structural Determination by Single-particle Cryo-electron Microscopy
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开放式和封闭式的人类TRPML1通道结构

Philip Schmiege1,2, Michael Fine3, Günter Blobel1

  • 1Laboratory of Cell Biology, Howard Hughes Medical Institute, The Rockefeller University, New York, New York 10065, USA.

Nature
|October 12, 2017
PubMed
概括

研究人员揭示了关闭状态和开放状态的暂时受体潜在粘脂蛋白1 (TRPML1) 通道的结构. 这为信号传递,溶解体功能和IV型粘脂症提供了洞察力.

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Expression and Purification of the Human Lipid-sensitive Cation Channel TRPC3 for Structural Determination by Single-particle Cryo-electron Microscopy
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科学领域:

  • 结构生物学
  • 分子生物学
  • 细胞生物学

背景情况:

  • 过渡性受体潜在粘脂蛋白1 (TRPML1) 是一种释放的通道,对溶解体信号传递和恒温至关重要.
  • TRPML1的功能障碍会导致IV型粘脂症,这是一种严重的溶酶体储存障碍.

研究的目的:

  • 在封闭和开放状态下确定全长人体TRPML1的高分辨率结构.
  • 阐明TRPML1通道调节和激活的分子机制.
  • 提供关于IV型粘脂症的结构基础的见解.

主要方法:

  • 使用电子冷显微镜 (cryo-EM) 来获得人类TRPML1的结构.
  • 在pH7.0的ap (闭合) 状态和pH6.0的agonist- bound (开放) 状态下确定结构.

主要成果:

  • 在高分辨率 (3.72 Å和3.49 Å) 解析了人类TRPML1的两个不同的冷EM结构.
  • 由S5,S6螺旋和孔螺旋1中的特定残留物形成的独特的疏水腔被确定为激素结合部位.
  • 道开放涉及下门的扩张和孔螺旋1的结构转移.

结论:

  • 这项研究揭示了TRPML通道的调节机制及其激活过程.
  • 这些发现提供了对粘脂类型IV病变的分子理解.
  • 这项工作有助于更好地理解TRP通道的功能和调节.