A novel function for translation initiation factor eIF5

蛋白质之间的相互作用调节细胞的基本功能，确保它们能够在正确的时间和地点生长和执行任务。细胞内的每一种蛋白质就像是复杂机器中的一块。在机器中，每个部件必须处于正确的位置，并在正确的时间与其他部件协调工作，机器才能正常运行。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组件的相互作用来改变其功能和/或位置。许多蛋白质在由蛋白质组成的复合体中或与其他细胞成分(例如，脂类、DNA或小分子)一起作用，以协调共同的功能。与这一提议相关的一组蛋白质需要在每个细胞中制造(或合成)所有新的蛋白质。这些被称为“蛋白质合成因子”。因此，了解蛋白质合成因子是如何发挥作用并相互作用的，对于了解蛋白质是如何在所有有机体的所有细胞中合成的是基本的。通过改善我们对正常细胞中蛋白质合成等过程的理解，它可以帮助科学家了解这一过程发生变化的疾病，或者病毒等感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。在这项提议之前的工作中，我们已经确定了两种蛋白质合成因子之间的一种新的复合体，称为eIF2和eIF5。这就引出了对这种复合体功能的假设，我们打算在这里使用‘试管中’纯化蛋白质的生化实验和以酵母细胞作为模型简单细胞系统的遗传实验相结合的方法来评估，以了解这种相互作用对于蛋白质合成的机制和调节的生物学意义。

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 have identified a novel complex between two protein synthesis factors known as eIF2 and eIF5. This has lead to a hypothesis for the function of this complex which we intend to assess here using a combination of biochemical experiments with purified proteins 'in the test-tube' and genetic experiments using yeast cells as a model simple cell system to understand the biological significance of this interaction for the mechanism and regulation of protein synthesis.