Sulfated Polysaccharides as a Fighter with Protein Non-Physiological Aggregation: The Role of Polysaccharide Flexibility and Charge Density

Proteins can lose native functionality due to non-physiological aggregation. In this work, we have shown the power of sulfated polysaccharides as a natural assistant to restore damaged protein structures. Protein aggregates enriched by cross-beta structures are a characteristic of amyloid fibrils related to different health disorders. Our recent studies demonstrated that model fibrils of hen egg white lysozyme (HEWL) can be disaggregated and renatured by some negatively charged polysaccharides. In the current work, using the same model protein system and FTIR spectroscopy, we studied the role of conformation and charge distribution along the polysaccharide chain in the protein secondary structure conversion. The effects of three carrageenans (kappa, iota, and lambda) possessing from one to three sulfate groups per disaccharide unit were shown to be different. kappa-Carrageenan was able to fully eliminate cross-beta structures and complete the renaturation process. iota-Carrageenan only initiated the formation of native-like beta-structures in HEWL, retaining most of the cross-beta structures. In contrast, lambda-carrageenan even increased the content of amyloid cross-beta structures. Furthermore, kappa-carrageenan in rigid helical conformation loses its capability to restore protein native structures, largely increasing the amount of amyloid cross-beta structures. Our findings create a platform for the design of novel natural chaperons to counteract protein unfolding.

Automated summary

This study demonstrates the potential of sulfated polysaccharides as natural assistants in restoring damaged protein structures, particularly in eliminating cross-beta structures associated with amyloid fibrils. The effects of different types of polysaccharides on protein secondary structure conversion vary depending on their conformation and charge distribution along the chain.