Signal Hypothesis

Signal sequence/peptide (N端信号序列 / 信号肽)
Signal recognition particles SRP (信号识别颗粒)
SRP receptors/docking proteins (信号识别颗粒受体 / 停泊蛋白)
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signal peptide

包含N-terminal,hydrophobic core,C-terminal,信号肽酶会切掉信号肽
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SRP

其中有蛋白质与RNA,有两个区域signal peptide recognition domain and ribosome binding domain
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Translocon 易位子

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SRP receptor specifically bind to SRP

Signal peptidase (信号肽酶)
ER luminal腔内 proteolytic水解 enzyme,专门切掉并降解信号肽

internal sequences

N-terminal signal peptide 是起始转移序列

stop-transfer anchor STA,这种序列可以让转移停止,让蛋白质卡在细胞膜上👇
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Multi-pass transmembrane proteins, containing multiple start transfer sequence and multiple STA sequence👇
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Synthesis of Secretory Proteins (Cotranslational translocation共翻译易位)

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  1. 刚开始游离的核糖体合成出大概80个氨基酸的片段,然后N-terminal ER signal sequence binds to SRP,肽链延申暂时停止
  2. SRP bind to SRP receptor,attaches the ribosomepeptide complex to the ER
  3. translocon 移位子 transfers the growing polypeptide chain across the ER membrane
  4. SRP dissociate from the signal sequence and ribosome, returns to the cytoplasmic matrix for reuse
  5. Peptide begins to synthesize again and translocate into ER lumen. Signal peptidase cleave signal sequence
  6. Completed polypeptide is released into ER lumen, ribosome is released and translocon close

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Pathways of Protein Sorting

cotranslational translocation 左
post-translational translocation 右
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Types of Protein Sorting

  1. Transmembrane transport (蛋白质的跨膜转运)
    Cotranslational translocation
    Post-translational translocation

  2. Vesicular transport (膜泡运输)
    从内质网到高尔基,再到其他部位
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  3. Gated transport (选择性门控转运)
    Transport of proteins through nuclear pore complexes 核孔复合体
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  4. Protein transport in cytoplasmic matrix (细胞质基质中蛋白质的转运)
    cytoskelton上的蛋白背着走

Protein Sorting to Mitochondria

in the post-translational transport pathway

外膜上有个TOM complex
内膜上有个TIM complex

有三种去处

  1. Protein Sorting from Cytoplasmic Matrix to Mitochondrial Matrix 到最里面
  2. Protein Sorting from Cytoplasmic Matrix to the Mitochondrial Inner Membrane 到内膜
  3. Protein Sorting from Cytoplasmic Matrix to Mitochondrial Intermembrane Space 到膜间隙

到里面
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到内膜
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到膜间隙
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Protein Sorting to Peroxisomes

signal sequence在C端

通过complex of peroxins过氧化物酶复合物把胞质里的蛋白转运进去

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