通过近距离特异性核糖体造型揭示了ER共翻译转位的原理
Calvin H Jan1, Christopher C Williams1, Jonathan S Weissman2
1These authors contributed equally to this work.
概括
这项研究揭示了蛋白质如何在特定的细胞位置合成,使用一种新的核糖体分析方法. 它显示大多数分泌蛋白质在合成过程中进入细胞内膜网 (ER),不同类型的蛋白质有不同的机制.
科学领域:
- 细胞生物学 细胞生物学
- 分子生物学分子生物学
- 生物化学 生物化学
背景情况:
- 局部蛋白质合成对于建立特定的亚细胞环境至关重要.
- 在定义的位置理解翻译是细胞功能的关键.
研究的目的:
- 开发一种可通用的方法,用于分析特定亚细胞位置的翻译.
- 为了研究酵母和哺乳动物内质网膜 (ER) 中的蛋白质合成和转位.
主要方法:
- 开发了一个近距离特定的核糖体分析策略.
- 应用了该方法来分析酵母和哺乳动物细胞在ER的翻译.
主要成果:
- 大多数分泌蛋白都经历同翻译转移到ER.
- 不同的转位子复合体在不同的合成阶段参与新生链.
- 一个蛋白质子集使用Sec66依赖的路径,具有循环信号序列.
- 核糖体在翻译后迅速交换成细胞体.
结论:
- 开发的方法可以在定义的亚细胞区内进行全球翻译分析.
- 独特的转位机制确保了蛋白质对ER的高效转换性招募.
- 结果提供了对蛋白质向和合成调节的见解.
相关概念视频
Cotranslational Protein Translocation
11.2K
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...
11.2K
Post-translational Translocation of Proteins to the RER
8.2K
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...
8.2K
Ribosome Profiling
4.4K
Ribosome profiling or ribo-sequencing is a deep sequencing technique that produces a snapshot of active translation in a cell. It selectively sequences the mRNAs protected by ribosomes to get an insight into a cell’s translation landscape at any given point in time.
Applications of ribosome profiling
Ribosome profiling has many applications, including in vivo monitoring of translation inside a particular organ or tissue type and quantifying new protein synthesis levels.
The technique...
Applications of ribosome profiling
Ribosome profiling has many applications, including in vivo monitoring of translation inside a particular organ or tissue type and quantifying new protein synthesis levels.
The technique...
4.4K
Directing Proteins to the Rough Endoplasmic Reticulum
18.5K
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...
18.5K
Protein Translocation Machinery on the ER Membrane
7.5K
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...
7.5K
Termination of Translation
29.1K
The large ribosomal subunit has several important structures essential to translation. These include the peptidyl transferase center (PTC) - which is the site where the peptide bond is formed - and a large, internal, water-filled tube through which the nascent polypeptide moves. This latter structure is called the Peptide Exit Tunnel, and it begins at the PTC and spans the body of the large ribosomal subunit. During translation, as the nascent polypeptide chain is synthesized, it passes through...
29.1K


