核糖体结合的Hsp70同源Ssbb的共翻译周期
Ying Zhang1, Lorenz Grundmann2,3, Leonie Vollmar4,5
1Institute of Biochemistry and Molecular Biology, ZBMZ, Faculty of Medicine, University of Freiburg, Freiburg, Germany.
Nature communications
|January 16, 2026
概括
核糖体关联复合体 (RAC) 和Hsp70伴侣Ssb在翻译过程中协调蛋白质折叠. 新的冷EM结构揭示了Ssb如何与核糖体结合,以捕获新生链,以便进行共翻译折叠.
科学领域:
- 分子生物学分子生物学
- 结构生物学 结构生物学
- 生物化学 生物化学
背景情况:
- 同转移的蛋白质折叠对于细胞功能至关重要.
- 在真核生物中,Hsp70护卫体和与核糖体相关的复合体 (RAC) 是关键参与者.
- 连接Hsp70功能与翻译的机制尚未完全理解.
研究的目的:
- 阐明Hsp70 (Ssb) 与核糖体相互作用的结构基础.
- 了解RAC在协调Hsp70功能与新生链合成中的作用.
- 揭示Hsp70是如何促进共翻译蛋白折叠的.
主要方法:
- 低温电子显微镜 (cryo-EM) 用于确定核糖体结合酵母Hsp70 Ssb.的结构.
- 生物化学测试. 生物化学测试.
- 突变分析. 突变分析.
主要成果:
- 确定了Rpl25/uL23作为Ssb.的特定核糖体结合部位.
- 可视化了Ssb与模型新生的多链的相互作用.
- 划出了依赖RAC的周期定位Ssb在核糖体道出口附近.
- 显示Ssb可以在ATP水解时经历构造变化,而不会受到硬质障碍.
结论:
- 这项研究提供了对Hsp70-核糖体相互作用在共翻译折叠过程中的结构性见解.
- 这种依赖于RAC的循环有助于有效地捕获和折叠新生的链条.
- Ssb的定位允许有效的基板结合和形状灵活性.
相关概念视频
Cotranslational Protein Translocation
9.6K
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...
9.6K
Post-translational Translocation of Proteins to the RER
7.5K
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...
7.5K
Bacterial Protein Maturation
470
Bacterial protein maturation is a tightly regulated process that ensures newly synthesized polypeptides achieve correct functional conformations. This maturation involves a series of modifications, folding events, and quality control steps, often assisted by specialized chaperone proteins.N-Terminal ModificationsThe maturation of bacterial polypeptides begins cotranslationally as the polypeptide exits the ribosome. The first amino acid, N-formylmethionine (fMet), is typically modified at the...
470
Insertion of Single-pass Transmembrane Proteins in the RER
16.8K
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...
16.8K
Directing Proteins to the Rough Endoplasmic Reticulum
17.1K
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...
17.1K
Energy to Drive Translocation
2.7K
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...
Generally, polypeptides are unfolded by two distinct...
2.7K


