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Interaction between translation factor eIF2gamma and its regulatory proteins

翻译因子 eIF2gamma 与其调节蛋白之间的相互作用

基本信息

批准号：
BB/F013272/1
负责人：
Graham Pavitt
金额：
$ 50.35万
依托单位：
University of Manchester
依托单位国家：
英国
项目类别：
Research Grant
财政年份：
2008
资助国家：
英国
起止时间：
2008 至无数据
项目状态：
已结题

来源：
https://gtr.ukri.org/projects?ref=BB%2FF013272%2F1
关键词：
Interaction between translation factor eIF2gamma

项目摘要

Interactions between proteins modulate essential functions of cells ensuring that they can grow and perform their tasks at the correct time and place. Each protein within a cell is like a piece within a complex machine. In a machine each part must be in the correct place and act at the correct time in concert with the other parts for the machine to function properly. The same is true for proteins within cells, but unlike most machines and their parts, proteins are continually renewed, move and can be modified by interaction with many other cell components to alter their function and/or location. Many proteins act together within complexes composed of proteins or with other cell components (lipids, DNA or small molecules for example) to coordinate a common function. One group of proteins relevant to this proposal is required make (or synthesize) all new proteins in each cell. These are called 'protein synthesis factors'. Understanding how protein synthesis factors function and interact with each other is therefore fundamental to understanding how proteins are made in all cells in all organisms. By improving our understanding how processes such as protein synthesis work in normal cells it can help scientists understand diseases in which this process is altered, or how infectious agents such as viruses are able to hijack plant, animal or human cells and cause infectious diseases. In work leading up to this proposal we identified a novel interaction between two protein synthesis factors known as eIF2 and eIF2B that is critical for protein synthesis. Mutations in eIF2B that impair this interaction are lethal in a yeast cellular model. We propose to study where on the surface of eIF2 is important for this interaction and to compare this with binding to eIF5, another important ligand for eIF2. We intend to study these interactions using a combination of genetic experiments using yeast cells as a model simple cell system and biochemical experiments with purified proteins in test-tubes to understand the biological significance of these interactions for the mechanism and regulation of protein synthesis.

蛋白质之间的相互作用调节细胞的基本功能，确保它们可以在正确的时间和地点生长和执行任务。细胞内的每一个蛋白质都像是复杂机器中的一个零件。在机器中，每个部件都必须在正确的位置，并在正确的时间与其他部件一起工作，以使机器正常工作。细胞内的蛋白质也是如此，但与大多数机器及其部件不同的是，蛋白质不断更新，移动，并可以通过与许多其他细胞成分的相互作用来改变它们的功能和/或位置。许多蛋白质在由蛋白质组成的复合物中或与其他细胞组分（例如脂质、DNA或小分子）一起作用以协调共同的功能。与此相关的一组蛋白质需要在每个细胞中制造（或合成）所有新蛋白质。这些被称为“蛋白质合成因子”。因此，了解蛋白质合成因子的功能和相互作用对于了解蛋白质在所有生物体的所有细胞中是如何产生的至关重要。通过提高我们对蛋白质合成等过程如何在正常细胞中工作的理解，它可以帮助科学家了解这一过程被改变的疾病，或者病毒等传染性病原体如何能够劫持植物，动物或人类细胞并导致传染病。在导致这一提议的工作中，我们确定了两种蛋白质合成因子eIF 2和eIF 2B之间的新型相互作用，这对蛋白质合成至关重要。在酵母细胞模型中，损害这种相互作用的eIF 2B突变是致命的。我们建议研究在eIF 2的表面上是重要的这种相互作用，并将其与eIF 5，eIF 2的另一个重要配体结合进行比较。我们打算研究这些相互作用，使用酵母细胞作为模型的简单细胞系统的遗传实验和生物化学实验与纯化的蛋白质在试管中的组合，以了解这些相互作用的蛋白质合成的机制和调节的生物学意义。