Exploration of membrane binding of α‐synuclein through Site Based Spin Labeling

Abstract

Neurodegenerative conditions, including Alzheimer's and Parkinson's disease, are becoming more prevalent in the aging population, and one of the main perpetrators behind these symptoms is the protein α‐synuclein (α‐syn). The cytosolic neural protein has a role in neurotransmitter transport within cells through membrane binding to intracellular vesicles. It is strongly linked to Parkinson's disease as a result of the A30P, E46K, and A53T point mutations, which are believed to cause α‐syn aggregation. These point mutations disrupt the formation of amphipathic α‐helices that directly bind to the vesicle surface. To gain further information on the membrane binding tendencies of α‐syn, each of these mutations, as well as a neutrally mutated C‐terminal tail (CTT), is being separately tested using site directed spin labeling and electron paramagnetic resonance (EPR) spectroscopy. The normally negatively charged CTT is the only region of the protein that does not directly contact the phospholipids during the membrane binding. Each of the mutant proteins' interactions with synthesized lipid vesicles will confirm the known malfunctions of the Parkinson's mutations, in addition to expanding of knowledge of the C‐terminal tail and its function in the membrane binding process. Results and analysis from the EPR spectroscopy are currently still being compiled. It is expected that each of the Parkinson's mutations and neutrally mutated CTT will decrease α‐syn membrane binding. These, or other conclusions from the analysis, can provide more information on the uncommonly studied α‐synuclein CTT and a basis on which to continue research for future undergraduate biochemistry students at Westminster College.Support or Funding InformationWestminster College Drinko Center Undergraduate Research GrantThis abstract is from the Experimental Biology 2018 Meeting. There is no full text article associated with this abstract published in The FASEB Journal.