通过线粒体Yme1蛋白酶识别小的Tim陪伴体
Mariella Quispe-Carbajal1, Lauren Todd1, Steven E Glynn1
1Department of Biochemistry and Cell Biology, Stony Brook University, Stony Brook, NY, USA.
bioRxiv : the preprint server for biology
|August 8, 2025
概括
酵母蛋白酶Yme1通过识别其灵活的N端区域来降解线粒体蛋白Tim10. 降解仅发生在Tim10之后.
科学领域:
- 线粒体生物学 线粒体生物学
- 蛋白质降解 蛋白质降解
- 蛋白酶的功能是保护酶的功能.
背景情况:
- Yme1是一种依赖ATP的蛋白酶,对线粒体功能至关重要.
- 在线粒体膜间空间中Yme1对基质的选择尚不清楚.
- 蒂姆10是小蒂姆陪伴组合的一个子单元,是已知的Yme1基质.
研究的目的:
- 通过Yme1.1.调查基质选择的分子机制.
- 阐明Yme1如何结合和降解小的Tim蛋白,特别是Tim10.
- 了解二硫化物键和蛋白质折叠在Yme1介导降解中的作用.
主要方法:
- 生物化学测定 生物化学测定
- 生物物理技术 生物物理技术
- 蛋白质与蛋白质相互作用的分析.
- 基质结合和降解研究研究.
主要成果:
- 通过高亲和度相互作用,Yme1优先结合Tim10而不是其他小的Tim蛋白.
- 蒂姆10的N端""对于最初的Yme1结合至关重要.
- 基板展开暴露了额外的结合点,增强了Yme1的参与.
- 酵母Yme1识别了人类的正义词TIMM13,表明了保存的识别.
- Yme1 结合了组装的 Tim9-Tim10 复合体,但不是通过 Tim10 N-终端区域.
结论:
- 在整个生命周期中,Yme1监测Tim10的折叠状态.
- 降解是由Tim10的二硫化物键的破坏引起的.
- 这些发现揭示了由Yme1.1进行基质选择和降解的保存机制.
相关概念视频
Mitochondrial Precursor Proteins
2.6K
Mitochondrial precursors are partially unfolded or loosely folded polypeptide chains. Newly synthesized precursors are inhibited from spontaneously folding into their native conformation by the cytosolic chaperones, heat shock proteins 70 (Hsp70), and mitochondrial import stimulation factors (MSFs). Precursors bound to MSFs are guided to the TOM70-TOM37 receptors, while precursors bound to Hsp70 chaperones are targetted to TOM20-TOM22 receptor complexes.
Most of the mitochondrial...
Most of the mitochondrial...
2.6K
Translocation of Proteins into the Mitochondria
3.2K
Mitochondrial precursors are translocated to the internal subcompartments via independent mechanisms involving distinct protein machineries called translocases.
Sorting of outer membrane proteins:
Mitochondrial outer membrane proteins are of two types: the transmembrane, beta-barrel porins, and the membrane-anchored, alpha-helical proteins. Beta-barrel porin precursors are translocated by the TOM complex and inserted into the outer mitochondrial membrane by the SAM complex. In contrast,...
Sorting of outer membrane proteins:
Mitochondrial outer membrane proteins are of two types: the transmembrane, beta-barrel porins, and the membrane-anchored, alpha-helical proteins. Beta-barrel porin precursors are translocated by the TOM complex and inserted into the outer mitochondrial membrane by the SAM complex. In contrast,...
3.2K
Mitochondrial Protein Sorting
4.4K
Mitochondria are double-membrane organelles of the eukaryotes involved in cellular metabolism, signaling, ATP synthesis, and programmed cell death. Each of these processes requires specific proteins and enzymes that must be correctly sorted to the right mitochondrial subcompartment for the proper functioning of the organelle.
Most of these mitochondrial proteins are encoded by the nucleus and imported to the mitochondria as unfolded or loosely folded precursors. Mitochondrial precursors...
Most of these mitochondrial proteins are encoded by the nucleus and imported to the mitochondria as unfolded or loosely folded precursors. Mitochondrial precursors...
4.4K
Protein Transport into the Inner Mitochondrial Membrane
4.1K
Nuclear encoded mitochondrial precursors are imported to the inner membrane in a multistep process involving two separate translocons, TIM22 and TIM23. TIM23 is a cation-selective pore that remains closed by the N terminal segment of the protein. Negative charges on the TIM23 act as a receptor for the incoming precursor, pulling the positively charged matrix-targeting sequence for peptide insertion and translocation.
Transport of mitochondrial precursors across the TIM23 channel is driven by...
Transport of mitochondrial precursors across the TIM23 channel is driven by...
4.1K
Energy to Drive Translocation
2.1K
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...
2.1K
Molecular Chaperones and Protein Folding
18.4K
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...
18.4K


