Characterizing the Lipid Membrane-Bound Structures of Peripheral Membrane Proteins

A complex set of cellular processes regulates the binding of peripheral membrane proteins to lipid membranes to allow for intercellular communication and function. Two members of this family are α-synuclein and the transmembrane immunoglobulin and mucin domain-containing protein-3 (TIM3), where the lipid-binding properties of the two proteins play a role within Parkinson's Disease and the immune response, respectively. We approach our investigations into these two systems through a biophysical characterization of the direct components involved in the protein:lipid interactions, using a range of techniques, including tryptophan fluorescence spectroscopy, CD, NMR, fluorescence polarization, MD, and X-ray reflectivity. Through our methods and corresponding mathematical frameworks we are able to uncover specific, molecular details of the underlying systems, providing insight into structural features of the proteins and their lipid membrane-binding behaviors. Ultimately, the work in this thesis aims to capture the utility of biophysical characterization in furthering our understanding of protein:lipid interactions and corresponding disease states.