NMR studies on lipid-peptide co-aggregation between ganglioside-containing membranes and α-synuclein

Sammanfattning: This topic of this thesis is how the presence of biomembrane molecules affect the behavior of a protein related to Parkinson’s disease in a simplified (compared to in the cell) model system.Lipids are fat molecules that make up the biological barriers in our body that control transport of essential molecules in and out of the cell and create an environment where membrane proteins can perform their functions. Some types of lipids can also act as surface recognition molecules, which communicate with other molecules outside of the cell such as proteins, toxins and viruses. Lipids are amphiphilic, which is crucial for their functions. That they are amphiphilic means that they have a part that is hydrophilic (water-loving) and another part that is hydrophobic (water-hating). This leads to the formation of self-assembled lipid structures in water, where hydrophilic parts shield the hydrophobic parts from water. The lipid bilayer of cell membranes is an example of one such self-assembled structure.Proteins are complex molecules that perform most of the functions in cells, such as promoting and regulating biochemical reactions. Proteins assume their 3- dimensional structure through self-assembly and finding the right structure is crucial for their function. In some cases, this process can be disturbed which can lead to pathological conditions. In the case of Parkinson’s disease, the protein a-synuclein assembles into highly ordered fibrils which end up in characteristic, large aggregates called Lewy bodies. It is not known exactly how these aggregates affect disease, but emerging evidence suggests that the process is affected by the presence of lipid membranes. Because both lipids and proteins self-assemble into their functional forms, it is possible that they can also co-assemble into mixed lipid-protein aggregates with new properties, which may be important in understanding the progression into disease.To investigate this type of lipid-protein aggregation process, we mainly used an experimental technique called nuclear magnetic resonance spectroscopy. This technique uses radiofrequency irradiation of a sample and exploits the magnetic properties of nuclei to gain information on the composition, dynamics and structure of molecules at the atomic level.