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

Area of Science:

• Biochemistry
• Neuroscience
• Protein Chemistry

Background:

• S100A9 is a pro-inflammatory protein that co-aggregates with proteins in amyloid plaques.
• Alpha-synuclein (α-syn) aggregation is central to Parkinson's disease pathogenesis.
• Limited data exist on the cross-interaction between S100A9 and α-syn and its impact on aggregation.

Purpose of the Study:

• To investigate the interaction between S100A9 and α-syn.
• To understand how this interaction affects the aggregation kinetics and structure of α-syn.
• To utilize 19F NMR spectroscopy as a tool to study protein-protein interactions and aggregation.

Main Methods:

• Solution 19F NMR spectroscopy.
• 2D 15N-1H HSQC NMR spectroscopy.
• Studied aggregation properties of S100A9 and α-syn.

Main Results:

• Identified specific regions of interaction between α-syn and S100A9.
• These interaction sites are crucial for the initial steps of α-syn aggregation.
• Demonstrated 4-fluorophenylalanine labeling in α-syn as a sensitive probe for studying interactions and aggregation via 19F NMR.

Conclusions:

• S100A9 directly interacts with α-syn, influencing its aggregation pathway.
• The findings provide insights into the molecular mechanisms underlying α-syn aggregation in the context of neurodegenerative diseases.
• 19F NMR is a valuable technique for probing protein-protein interactions and aggregation dynamics.