Protein Interactions from the Molecular to the Domain Level

Abstract

The basic unit of life is the cell, from single-cell bacteria to the largest creatures on the planet. All cells have DNA, which contains the blueprint for proteins. This information is transported in the form of messenger RNA from the genome to ribosomes where proteins are produced. Proteins are the main functional constituents of the cell, they usually have one or several functions and are the main actors in almost all essential biological processes. Proteins are what make the cell alive. Proteins are found as solitary units or as part of large complexes. Proteins can be found in all parts of the cell, the most common place being the cytoplasm, a central space in all cells. They are also commonly found integrated into or attached to various membranes. Membranes define the cell architecture. Proteins integrated into the membrane have a wide number of responsibilities: they are the gatekeepers of the cell, they secrete cellular waste products, and many of them are receptors and enzymes. The main focus of this thesis is the study of protein interactions, from the molecular level up to the protein domain level. In paper I use reoccurring local protein structures to try and predict what sections of a protein interacts with another part using only sequence information. In papers II and III we use a randomization approach on a membrane protein motif that we know interacts with a sphingomyelin lipid to find other candidate proteins that interact with sphingolipids. These are then experimentally verified as sphingolipid-binding. In the last paper, paper IV, we look at how protein domain interaction networks overlap and can be evaluated.At the time of the doctoral defense, the following paper was unpublished and had a status as follows: Paper 3: Manuscript.</p