Interactions between S100A9 and Alpha-Synuclein: Insight from NMR Spectroscopy

S100A9 is a pro-inflammatory protein that co-aggregates with other proteins in amyloid fibril plaques. S100A9 can influence the aggregation kinetics and amyloid fibril structure of alpha-synuclein ([Formula: see text]-syn), which is involved in Parkinson’s disease. Currently, there are limited data regarding their cross-interaction and how it influences the aggregation process. In this work, we analyzed this interaction using solution [Formula: see text] F and 2D (15)N–(1)H HSQC NMR spectroscopy and studied the aggregation properties of these two proteins. Here, we show that [Formula: see text]-syn interacts with S100A9 at specific regions, which are also essential in the first step of aggregation. We also demonstrate that the 4-fluorophenylalanine label in alpha-synuclein is a sensitive probe to study interaction and aggregation using [Formula: see text] F NMR spectroscopy.