线粒体前序列转位酶:在TOM绑定和运动招募之间切换涉及Tim21和Tim17
Agnieszka Chacinska1, Maria Lind, Ann E Frazier
1Institut für Biochemie und Molekularbiologie, Universität Freiburg, Hermann-Herder-Strasse 7, D-79104 Freiburg, Germany.
Cell
|March 31, 2005
概括
该TIM23复合体动态切换合作伙伴,以控制蛋白质进口到线粒体. Tim21促进了外膜准,而Tim17通过与PAM电机相互作用来调解矩阵导入.
科学领域:
- 线粒体蛋白质的进口
- 内线粒体膜的内部线粒体膜.
- 蛋白质转位机器
背景情况:
- TIM23复合体是蛋白质进口到线粒体的核心.
- 它调解蛋白质从外层TOM复合体到内膜或基质的运输.
- 协调这些不同的途径的机制尚不清楚.
研究的目的:
- 为了阐明TIM23复合体在蛋白质进口中的调控机制.
- 为了确定参与指导前蛋白到内膜与矩阵之间的因素.
- 了解TIM23复合体如何在不同的进口路径之间切换.
主要方法:
- 确定TIM23综合体的交互合作伙伴.
- 使用酵母遗传学分析蛋白质与蛋白质相互作用的分析.
- 研究Tim21和Tim17在蛋白质转位中的作用.
主要成果:
- 蒂姆21与TOM复合体相互作用,促进内膜插入.
- 矩阵转位需要一个无Tim21的TIM23复合体与PAM电机结合.
- 蒂姆17在促进内膜插入和通过帕姆18招募PAM电机方面发挥了双重作用.
结论:
- 该TIM23复杂的功能作为一个动态实体,在TOM绑定和PAM绑定之间切换.
- Tim21和Tim17是协调这些动态交换机的关键监管机构.
- 这种动态机制允许精确协调蛋白质进口通路进入线粒体.
相关概念视频
Mitochondrial Protein Sorting
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...
Mitochondrial Precursor Proteins
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 precursors...
Most of the mitochondrial precursors...
Translocation of Proteins into the Mitochondria
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,...
Energy to Drive Translocation
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...
Protein Transport into the Inner Mitochondrial Membrane
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...
Cotranslational Protein Translocation
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...


