Interaction between translation factor eIF2gamma and its regulatory proteins

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。细胞内的每个蛋白质就像复杂机器中的一个部件。在机器中，每个部件必须在正确的位置和正确的时间与其他部件协同工作，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，蛋白质不断更新，移动，并可以通过与许多其他细胞成分相互作用来改变其功能和/或位置。许多蛋白质在由蛋白质或其他细胞成分（如脂质、DNA或小分子）组成的复合体中一起起作用，以协调共同的功能。与此建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如何发挥作用并相互作用是理解所有生物体中所有细胞如何制造蛋白质的基础。通过提高我们对蛋白质合成等过程如何在正常细胞中起作用的理解，它可以帮助科学家了解这一过程发生改变的疾病，或者病毒等传染性病原体如何能够劫持植物、动物或人类细胞并引起传染病。在提出这一建议的工作中，我们发现了两个蛋白质合成因子eIF2和eIF2B之间的一种新的相互作用，这对蛋白质合成至关重要。破坏这种相互作用的eIF2B突变在酵母细胞模型中是致命的。我们建议研究eIF2表面上对这种相互作用重要的位置，并将其与eIF2的另一个重要配体eIF5的结合进行比较。我们打算结合以酵母细胞为模型的简单细胞系统的遗传实验和试管中纯化蛋白的生化实验来研究这些相互作用，以了解这些相互作用对蛋白质合成机制和调控的生物学意义。

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 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.