High-Resolution NMR Study of Ligand and Ca2+ binding to the C-Terminal Region of α-Synuclein

Human α-synuclein (α-syn), an IDP implicated in several neurodegenerative diseases including Parkinson’s Disease, is composed of 140 amino acids organized into three regions: a positively charged N-terminal tail, a hydrophobic central region, and a negatively charged C-terminal region. The latter has been shown to interact with both small molecules and metal ions. In this study, we investigate the interaction between α-syn and Fasudil, a compound known to interact with the C-terminal part of α-syn and to delay the formation of its toxic aggregates. We also examine the modulatory role of calcium ions in this interaction. For our study we use a construct comprising αsyn residues 112–140 (C-α-syn).