Interaction between translation factor eIF2gamma and its regulatory proteins

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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.