伴侣和介导翻译和蛋白质折叠效率
bioRxiv : the preprint server for biology
|July 16, 2025
概括
同义词的mRNA变化通过影响翻译效率显著改变蛋白质水平. 这可能会压倒细胞的陪伴能力,影响蛋白质折叠平衡,并表明翻译和折叠的共同进化.
科学领域:
- 分子生物学分子生物学
- 蛋白质合成 蛋白质合成
- 细胞平衡是细胞的平衡.
背景情况:
- 从核糖体和结构元素形成中出现新生的蛋白质的同步是长期存在的问题.
- 动力学高效的翻译可能会导致蛋白质错误折叠和聚合,即使存在分子伴侣.
- 连接翻译效率和蛋白质折叠效率的分子机制尚不清楚.
研究的目的:
- 调查同名mRNA变化对翻译效率的直接影响.
- 为了确定翻译效率改变对蛋白质水平和细胞反应的影响.
- 阐明翻译效率,蛋白质折叠和细胞伴侣能力之间的关系.
主要方法:
- 使用核糖体分析来测量翻译效率.
- 使用蛋白质量测量来评估蛋白质水平.
- 分析了分子伴侣的细胞反应,特别是Escherichia coli*中的sigma 32 (σ32) 转录反应.
主要成果:
- 火路西法酶 (Luc) mRNA中的同义变化直接影响了其翻译效率,导致Luc蛋白水平的差异高达70倍.
- 通过σ32介导的细胞伴侣反应显示了和性质,尽管Luc蛋白质发生了很大的变化,但最多增加了约2倍.
- 当Luc mRNA表现出中间翻译效率时,s32反应对扰动最敏感.
结论:
- 伴侣和限制了细胞在面对高效翻译时维持蛋白质折叠平衡的能力.
- 翻译效率和蛋白质折叠效率似乎已经共同演变为相互敏感性.
- 这些发现提供了关于蛋白质合成速率和负责确保适当蛋白质折叠的细胞机制之间的复杂相互作用的见解.
更多相关视频
相关概念视频
Bacterial Protein Maturation
94
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...
94
Molecular Chaperones and Protein Folding
18.5K
The native conformation of a protein is formed by interactions between the side chains of its constituent amino acids. When the amino acids cannot form these interactions, the protein cannot fold by itself and needs chaperones. Notably, chaperones do not relay any additional information required for the folding of polypeptides; the native conformation of a protein is determined solely by its amino acid sequence. Chaperones catalyze protein folding without being a part of the folded protein.
The...
The...
18.5K
Improving Translational Accuracy
11.9K
Base complementarity between the three base pairs of mRNA codon and the tRNA anticodon is not a failsafe mechanism. Inaccuracies can range from a single mismatch to no correct base pairing at all. The free energy difference between the correct and nearly correct base pairs can be as small as 3 kcal/ mol. With complementarity being the only proofreading step, the estimated error frequency would be one wrong amino acid in every 100 amino acids incorporated. However, error frequencies observed in...
11.9K
Translational Regulation
104
Translational regulation in prokaryotes ensures efficient protein synthesis by controlling ribosome access to mRNA. This regulation is mediated by secondary RNA structures, including translational riboswitches, RNA thermometers, and small RNAs (sRNAs), which respond to intracellular and environmental signals to modulate gene expression.Translational RiboswitchesRiboswitches in the leader region of mRNAs can regulate translation by altering the accessibility of the Shine-Dalgarno (SD) sequence,...
104
Cotranslational Protein Translocation
7.6K
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...
7.6K
Post-translational Translocation of Proteins to the RER
5.9K
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...
5.9K


