Complement Factor H and Simian Virus 40 bind the GM1 ganglioside in distinct conformations

Area of Science:

• Glycobiology
• Structural Biology
• Immunology

Background:

• Mammalian cell surfaces feature diverse glycan chains crucial for biological processes.
• Pathogens exploit cell-surface glycans for attachment and entry.
• GM1 ganglioside is a key monosialylated pentasaccharide acting as a protein ligand.

Purpose of the Study:

• To investigate the differential conformational selection of the GM1 ganglioside glycan when interacting with various lectins.
• To elucidate the specific GM1 conformation bound by complement Factor H (FH).

Main Methods:

• STD NMR (Saturation Transfer Difference Nuclear Magnetic Resonance)
• X-ray crystallography
• Molecular dynamics simulations (10 μs timescale)

Main Results:

• Complement Factor H (FH) binds a novel GM1 conformation distinct from those recognized by other lectins like SV40.
• The FH-bound GM1 conformation represents a Gibbs free energy minimum.
• This conformation exhibits poor NOE restraints, explaining its previous elusiveness in modeling.

Conclusions:

• Glycans exhibit conformational flexibility, enabling differential selection by interacting proteins.
• The discovery of the FH-bound GM1 conformation advances understanding of glycan-mediated recognition.
• Ensemble representations are necessary for accurately depicting glycan structures in complex interactions.