The β-reducing end in α(2-8)-polysialic acid constitutes a unique structural motif

Area of Science:

• Carbohydrate chemistry
• Structural biology
• Biophysics

Background:

• Structural characterization of α(2-8)-polysialic acid (polySia) in solution has been challenging.
• Previous studies focused on α-linked residues, neglecting terminal residue characteristics.

Purpose of the Study:

• To elucidate the structural and dynamic impact of the β-anomeric configuration at the reducing end of α(2-8)-polySia.
• To investigate the role of this terminal motif in polySia's interaction with antibodies.

Main Methods:

• Molecular dynamics (MD) simulations to predict hydrogen bond formation.
• Nuclear Magnetic Resonance (NMR) spectroscopy to detect the predicted hydrogen bond.
• Residual dipolar couplings and NOE-based distance measurements for structural analysis.

Main Results:

• A stable hydrogen bond was identified between the terminal β-anomeric hydroxyl group and the adjacent residue's carboxylate.
• This interaction defines a specific conformation with distinct hydration and charge patterns near the reducing end.
• The observed motif was found to be conserved in Sia oligosaccharides, impacting the structure of the first two residues of polySia.

Conclusions:

• The β-anomeric configuration at the reducing end of polySia creates a stable structural motif.
• This motif influences the overall structure and dynamics of α(2-8)-polysialic acid.
• The findings may explain the requirement of a specific polySia chain length for effective antibody binding.