在ER膜的翻译和蛋白质生物生成的可视化
Max Gemmer1, Marten L Chaillet1, Joyce van Loenhout1
1Structural Biochemistry, Bijvoet Center for Biomolecular Research, Utrecht University, Utrecht, The Netherlands.
Nature
|January 25, 2023
概括
研究人员可视化了内分泌网膜中的核糖体转移机制. 他们捕获了关键的中间体和相互作用, 揭示了蛋白质如何在本地环境中合成和处理.
科学领域:
- 细胞生物学
- 分子生物学
- 结构生物学
背景情况:
- 在ER膜中的核糖体-转移组合合成了大多数人体蛋白质.
- 在现场了解其组件的相互作用至关重要,但有限.
- 新生蛋白质的加工包括合成,转移,插入,糖化,折叠和二硫化键的形成.
研究的目的:
- 在分子分辨率下捕获mRNA转化和蛋白质成熟的快照.
- 阐明 ribo-translocon 机械元件在它们原生膜环境中的相互作用.
- 提供有关ER蛋白质生物生成的原子层次见解.
主要方法:
- 低温电子断层扫描
- 广泛的分类和数据分析
- 分子建模和结构确定
主要成果:
- 在扩展形状中确定了具有真核延长因子1a (eEF1a) 的转移前中间体.
- 观察到与信号或多通道跨膜蛋白专门的ER转位体有明显的多体结合.
- 确定了SEC61-TRAP-OSTA转位变体的近乎完整的原子模型,详细说明了TRAP相互作用.
- 检测到与寡糖转移酶复合体A (OSTA) 相关的辅因子,可能包括蛋白质异构酶.
结论:
- 在分子分辨率下可视化ER结合的多体和它们的协调下游机制.
- 提供了蛋白质合成和成熟过程中的核糖体-转基因复合体内的动态相互作用的见解.
- 揭示了专门的ER转位子,并确定了参与新生蛋白质加工的关键组件.
相关概念视频
Post-translational Translocation of Proteins to the RER
5.8K
A sizable fraction of proteins destined for ER are first synthesized in the cell cytosol and then transported across the ER membrane–a process called post-translational translocation. Similar to cotranslationally translocated proteins, these proteins also use the Sec translocon complex to enter the ER lumen.
Targeting proteins to the ER
Hsp40 and Hsp70 chaperone molecules bind the translated proteins in the cytosol to prevent their folding. The chaperone binding helps to keep the signal...
Targeting proteins to the ER
Hsp40 and Hsp70 chaperone molecules bind the translated proteins in the cytosol to prevent their folding. The chaperone binding helps to keep the signal...
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Cotranslational Protein Translocation
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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...
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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Directing Proteins to the Rough Endoplasmic Reticulum
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The organelle-specific signaling sequences direct proteins synthesized in the cytosol to their final destination like ER, mitochondria, peroxisomes, etc. Some of the proteins directed to ER are then trafficked via vesicles to other organelles within the cell or the extracellular environment through the Golgi complex. For example, the rough ER synthesizes soluble proteins for transportation to the lysosomes or secretion out of the cell. It can also synthesize transmembrane proteins that can...
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Insertion of Single-pass Transmembrane Proteins in the RER
6.9K
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...
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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Protein Translocation Machinery on the ER Membrane
4.8K
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...
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...
4.8K
The Endoplasmic Reticulum
15.1K
The endoplasmic reticulum or ER makes up for more than half of the membranes in a cell and accounts for 10% of total cell volume. It is also the primary protein and lipid synthesis factory for most cell organelles, such as the Golgi apparatus, lysosomes, secretory vesicles, and the plasma membrane. Despite being the most extensive and functionally complex subcellular organelle, ER was the last to be discovered. After years of deliberation, Keith Porter and George Palade in the year 1954,...
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