Specific binding of the chemokine platelet factor 4 to heparan sulfate.
Platelet factor 4 is a tetrameric heparin binding chemokine released from the alpha-granules of activated platelets. In this study we show that platelet factor 4 binds with high affinity and specificity to an approximately 9-kDa sequence in heparan sulfate, which it protects from degradation by heparinase enzymes. This protected fragment is enriched in N-sulfated disaccharides and iduronate 2-O-sulfate residues, the latter being important for binding to platelet factor 4. The major structural motif of the fragment appears to consist of a pair of sulfated domains positioned at both ends separated by a central mainly N-acetylated region. On the basis of these findings, we propose a model in which the heparan sulfate fragment wraps around the ring of positive charges on platelet factor 4 with the iduronate 2-O-sulfates within the sulfated domains binding strongly to lysine clusters on opposite faces of the tetramer.