Lysozyme's lectin-like characteristics facilitates its immune defense function.

Area of Science:

• Structural biology
• Immunology
• Microbiology

Background:

• Human lysozyme (HL) plays a role in innate immunity.
• Lipopolysaccharide (LPS) from Klebsiella pneumoniae O1 is a key component of this bacterium, often causing lung infections.
• Understanding HL-LPS interactions is crucial for developing new therapeutic strategies against bacterial infections.

Purpose of the Study:

• To elucidate the molecular mechanism of interaction between human lysozyme (HL) and Klebsiella pneumoniae O1 LPS.
• To characterize the binding sites and structural changes involved in HL-LPS recognition.

Main Methods:

• Surface plasmon resonance (SPR) to detect HL-LPS interactions.
• Nuclear magnetic resonance (NMR) spectroscopy to study pH-dependent structural rearrangements of HL.
• X-ray crystallography to determine the high-resolution structure of the HL-tetrasaccharide complex.

Main Results:

• HL binding to synthetic LPS fragments (disaccharides and tetrasaccharides) was confirmed.
• NMR revealed pH-dependent structural changes in HL upon disaccharide binding.
• Crystal structure showed LPS tetrasaccharide chains packing into HL's A, B, C, and D sites via hydrogen bonds and hydrophobic contacts, highlighting the role of specific residues (Glu35, Asp53, Trp63, Asp102).

Conclusions:

• The study identified specific residues crucial for HL binding to the LPS tetrasaccharide.
• A novel glycan-guided mechanism for bacterial cell wall recognition by lysozyme was proposed.
• These findings suggest a potential complementary role for HL in bacterial immune defense.