| Popis: |
To achieve homeostasis, the cell not only needs to control protein production, but it also needs to control the degradation of its current protein pools. This is achieved in part through the action of the ubiquitination machinery, which selectively recognizes unwanted proteins and facilitates their degradation. During cell growth, adaptation to environmental and metabolic changes require responsive mechanisms that can degrade proteins that are not physiologically relevant. This allows cells to stop the function of these proteins and recycles them into free amino acids to be used for generating new biological material. How the cell achieves the feat of selectively recognizing these unwanted proteins apart from the hundreds of thousands of other proteins is only beginning to be understood. In this dissertation, we provide new knowledge about a possible recognition mechanism that is used by the ubiquitination machinery in response to changes in nutrient levels in the cell. We focused on the homeostatic regulation of Ypq1, a yeast lysine transporter on the vacuole (yeast lysosome) membrane which is downregulated when cells are starved of lysine. This transporter is recognized by an E3 ubiquitin ligase adaptor, Ssh4. How Ssh4 coordinates with Ypq1 to sense lysine levels and lysine transport, and how these signals are translated into recognizable structural changes are detailed in this work. Furthermore, like Ypq1, many other lysosome membrane transporters are not well-understood. Here we also discuss some new tools to aid in studying membrane transporter function and regulation. |
