Heparin binding preference and structures in the fibroblast growth factor family parallel their evolutionary...

Area of Science:

• Biochemistry
• Evolutionary Biology
• Glycobiology

Background:

• Heparan sulfate (HS) interactions with extracellular proteins are crucial for biological regulation.
• The molecular specificity of protein-polysaccharide binding, particularly with fibroblast growth factors (FGFs), remains incompletely understood.

Purpose of the Study:

• To investigate the binding preferences of specific FGFs to modified heparins representing HS structures.
• To identify key lysine residues involved in FGF binding sites.
• To correlate FGF binding specificity with their phylogenetic relationships.

Main Methods:

• Differential scanning fluorimetry to measure FGF binding affinities to heparin libraries.
• Selective labeling techniques to identify lysine residues in FGF binding sites.
• Amino acid sequence alignment to construct the FGF phylogenetic tree.

Main Results:

• Six FGFs (FGF3, FGF4, FGF6, FGF10, FGF17, FGF20) showed distinct binding preferences for modified heparins.
• Specific lysine residues were identified in both primary and secondary binding sites of the studied FGFs.
• FGF binding selectivity and secondary binding site patterns mirrored the phylogenetic relationships within the FGF family.

Conclusions:

• The evolution of the FGF family and the development of complex animal body plans are linked to the diversification of HS binding specificity.
• Phylogenetic relationships provide a framework for understanding the evolution of FGF-heparan sulfate interactions.