Calcium-Dependent S100A8 Amyloid Fibril Formation via S100A1-Mediated Transient Interaction.

Area of Science:

• Biochemistry
• Neuroscience
• Protein Chemistry

Background:

• The S100 protein family plays roles in neuroinflammation, cardiac, and neurological functions.
• S100 proteins can aggregate in neuropathologies, contributing to dementia pathogenesis.
• S100A1 and S100A8 interactions and aggregation are poorly understood, unlike S100B and S100A9.

Purpose of the Study:

• To investigate the potential for S100A1 and S100A8 proteins to form heterodimers, interact, and coaggregate.
• To elucidate the role of calcium ions in these interactions and aggregation processes.

Main Methods:

• Utilized amyloid and protein-specific fluorescence detection.
• Employed electron-electron double resonance (EEDR) spectroscopy.
• Analyzed protein aggregation and fibril formation under varying calcium concentrations.

Main Results:

• Calcium ions are key drivers for S100A1 and S100A8 interactions and S100A8 amyloid aggregation.
• S100A1 remained largely stable, while S100A8 formed spherical or unspecific aggregates.
• Transient interactions between S100A1 and S100A8 facilitated worm-like amyloid fibril formation, regulated by calcium levels.
• High calcium concentrations stabilized both proteins, inhibiting aggregation.

Conclusions:

• S100A1 and S100A8 do not form stable heterodimers but exhibit transient interactions.
• Calcium ion concentration critically regulates the aggregation behavior of S100A8 and the coaggregation of S100A1/S100A8.
• This study enhances understanding of S100 protein interactions and aggregation relevant to neurological pathologies.