在核糖体上激活GTP水解的机制
Rebecca M Voorhees1, T Martin Schmeing1, Ann C Kelley1
1MRC Laboratory of Molecular Biology, Cambridge, UK, CB2 0QH.
概括
研究人员揭示了核糖体如何激活蛋白质合成中的GTP水解. 一个晶体结构显示延长因子Tu (EF-Tu) 在一个活跃的构造,至关重要的交付氨基酸-tRNAs.
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:
- 蛋白质合成依赖于诸如延长因子Tu (EF-Tu) 这样的瓜诺辛三酸酶 (GTPase) 因素.
- 在翻译过程中,EF-Tu将氨基酸转移RNA (tRNA) 传递给核糖体.
- 了解核糖体的GTPase激活是解读蛋白质合成调节的关键.
研究的目的:
- 阐明核糖体在转化性GTP酶中触发GTP水解的机制.
- 确定EF-Tu激活在核糖体上的结构基础.
主要方法:
- 使用X射线结晶学来确定结构.
- 使用GTP模拟器,EF-Tu和与核糖体结合的氨基-tRNA的结构被解析为3.2安格斯特姆.
主要成果:
- 观察到EF-Tu是在其活性构造中.
- 订购了EF-Tu的交换机I循环,并将催化定位为GTP水解.
- 鉴定出23S核糖体RNA的萨尔-子循环的histidine和A2662之间的保守相互作用对激活至关重要.
结论:
- 确定的结构为转化GTPases的激活机制提供了洞察力.
- 建议在核糖体上进行GTPase激活和水解的通用机制.
- 这一发现提高了我们对蛋白质合成复杂过程的理解.
相关概念视频
GTPases and their Regulation
Guanine nucleotide-binding proteins (G-proteins), also known as GTPases, are a superfamily of proteins that regulate many cellular processes, such as cell signaling, vesicular transport, and the regulation of cell shape and motility. Mutation or dysfunction of these proteins can lead to disease. There are around 40,000 known G-proteins that can broadly be classified into two groups ‒ small G-proteins consisting of a single domain and large multi-domain G-proteins.
Large G-proteins, also known...
Large G-proteins, also known...
GTPases and their Regulation
Guanine nucleotide-binding proteins (G-proteins), also known as GTPases, are a superfamily of proteins that regulate many cellular processes, such as cell signaling, vesicular transport, and the regulation of cell shape and motility. Mutation or dysfunction of these proteins can lead to disease. There are around 40,000 known G-proteins that can broadly be classified into two groups ‒ small G-proteins consisting of a single domain and large multi-domain G-proteins.
Large G-proteins, also known...
Large G-proteins, also known...
Activation and Inactivation of G Proteins
Heterotrimeric G proteins are guanine nucleotide-binding proteins. As the name suggests, heterotrimeric G proteins are composed of three subunits: alpha, beta, and gamma. They remain GDP-bound or GTP-bound inside the cells and switch between inactive/active states. The Gα subunit possesses the nucleotide-binding pocket that binds guanine nucleotides and switches between GDP or GTP-bound states. In contrast, the Gꞵ and Gγ subunits are always bound together with high affinity and are together...
Small GTPases - Ras and Rho
Ras and Rho are small monomeric GTPases that act downstream of receptor tyrosine kinase (RTK) and regulate various cellular processes. These GTPases switch between active and inactive states by binding to guanine nucleotides.
Three regulatory proteins control their activity:
Three regulatory proteins control their activity:
Rab Proteins
Rab proteins constitute the largest family of monomeric GTPases, of which 70 members are present in humans. Rab proteins and their effectors regulate consecutive stages of vesicle transport such as vesicle transport, docking, and fusion to the correct recipient membrane.
Rab proteins switch between a cytosolic, GDP-bound inactive state and a membrane-anchored, GTP-bound active state. By themselves, Rabs show slow rates of GDP/GTP exchange and GTP hydrolysis. Thus, Rab proteins are considered...
Rab proteins switch between a cytosolic, GDP-bound inactive state and a membrane-anchored, GTP-bound active state. By themselves, Rabs show slow rates of GDP/GTP exchange and GTP hydrolysis. Thus, Rab proteins are considered...
Mechanical Protein Functions
Proteins perform many mechanical functions in a cell. These proteins can be classified into two general categories- proteins that generate mechanical forces and proteins that are subjected to mechanical forces. Proteins providing mechanical support to the structure of the cell, such as keratin, are subjected to mechanical force, whereas proteins involved in cell movement and transport of molecules across cell membranes, such as an ion pump, are examples of generating mechanical force.


