通过HSP90-R2TP-TTT护送系统成熟和组装mTOR复合体:分子洞察力和机制
Andrés López-Perrote1, Marina Serna2, Oscar Llorca3
1Spanish National Cancer Research Centre (CNIO), Structural Biology Programme, Melchor Fernández Almagro 3, Madrid, Spain. aperrote@cnio.es.
Sub-cellular biochemistry
|July 4, 2024
概括
包括HSP90-R2TP-TTT在内的Rapamycin (mTOR) 护卫系统的机械性标对于组装活性mtORC1和mtORC2复合体至关重要. 该系统确保了mTOR功能在细胞生长和新陈代谢中的正确折叠和子单元结合.
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:
- 拉巴胺素的机械标 (mTOR) 是细胞生长,新陈代谢和增殖的中央调节者.
- mTOR在两个不同的复合体中运作,mTORC1和mTORC2,每个复合体都有独特的作用.
- 适当组装和激活mTOR复合体对于细胞平衡至关重要.
研究的目的:
- 审查目前对mTOR复杂组装所涉及的陪伴系统的理解.
- 阐明HSP90,R2TP和TTT复合体在mTOR成熟中的作用.
- 讨论有关mTORC1和mTORC2生物发生的相互作用,结构和机制.
主要方法:
- 关于mTOR复合组合和陪伴者相互作用的研究文献综述.
- 分析与mTOR,HSP90,R2TP和TTT相关的结构和机制数据.
- 关于mTORC1和mTORC2.2的陪伴辅助成熟的当前知识的综合.
主要成果:
- TELO2-TTI1-TTI2 (TTT) 综合体促进了mTOR的转换折叠.
- 结合HSP90,R2TP复合物促进了mTOR的组装和二元化,使其成为活跃的mtORC1和mtORC2复合物.
- 护航员系统确保了功能性mTOR复合体的正确形状和子单元的整合.
结论:
- 该HSP90-R2TP-TTT护送系统对于活跃的mTORC1和mTORC2.2的生物发生是不可或缺的.
- 了解这些陪伴机制,可以了解细胞生长和新陈代谢的调节.
- 这个系统的调节失调可能会对与异常细胞生长相关的疾病产生影响.
相关概念视频
Protein Complex Assembly
10.6K
Proteins can form homomeric complexes with another unit of the same protein or heteromeric complexes with different types. Most protein complexes self-assemble spontaneously via ordered pathways, while some proteins need assembly factors that guide their proper assembly. Despite the crowded intracellular environment, proteins usually interact with their correct partners and form functional complexes.
Many viruses self-assemble into a fully functional unit using the infected host cell to...
Many viruses self-assemble into a fully functional unit using the infected host cell to...
10.6K
mTOR Signaling and Cancer Progression
3.8K
The mammalian target of rapamycin or mTOR protein was discovered in 1994 due to its direct interaction with rapamycin. The protein gets its name from a yeast homolog called TOR. The mTOR protein complex in mammalian cells plays a major role in balancing anabolic processes such as the synthesis of proteins, lipids, and nucleotides and catabolic processes, such as autophagy in response to environmental cues, such as availability of nutrients and growth factors.
The mTOR pathway or the...
The mTOR pathway or the...
3.8K
PI3K/mTOR/AKT Signaling Pathway
3.5K
The mammalian target of rapamycin (mTOR) is a serine/threonine kinase that regulates growth, proliferation, and cell survival in response to hormones, growth factors, or nutrient availability. This kinase exists in two structurally and functionally distinct forms: mTOR complex 1 (mTORC1) and mTOR complex 2 (mTORC2). The first form (mTORC1) is composed of a rapamycin-sensitive Raptor and proline-rich Akt substrate, PRAS40. In contrast, mTORC2 consists of a...
3.5K
Molecular Chaperones and Protein Folding
17.9K
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...
17.9K
Cotranslational Protein Translocation
7.3K
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...
7.3K
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


