Biophysical analysis of sialic acid recognition by the complement regulator Factor H

Area of Science:

• Immunology
• Biochemistry
• Glycobiology

Background:

• Complement factor H (FH) regulates the complement alternative pathway (AP).
• FH possesses glycan binding sites, including one for α2-3-linked sialic acid, and binds C3b.
• The C3b binding site in FH may be occluded by intramolecular interactions involving sialylation.

Purpose of the Study:

• To investigate the sialylation of FH and identify sialic acid binding sites.
• To characterize sialic acid binding sites in FH and FH like-1 (FHL-1).
• To probe FH binding to the non-human sialic acid Neu5Gc.

Main Methods:

• Characterization of FH sialylation linkage types.
• Screening for sialic acid binding sites in FH and FHL-1.
• Assessment of FH binding to Neu5Gc.

Main Results:

• FH predominantly contains α2-6-linked sialic acid, not α2-3-linked.
• A single sialic acid binding site was identified in FH; FHL-1 has none.
• FH directly binds to Neu5Gc.

Conclusions:

• An intramolecular self-inhibition mechanism for FH via sialic acid binding is unlikely.
• FH's interaction with Neu5Gc supports the use of FH transgenic mice for complement-related disease research.