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.
Stringer
S E
SE
Cancer Research Campaign, Manchester, M20 9BX, United Kingdom.
Gallagher
J T
JT
D001665:Binding Sites; D019763:Heparin Lyase; D006497:Heparan Sulfate / Q000378:metabolism*; D010978:Platelet Factor 4 / Q000737:chemistry / Q000378:metabolism*; D011133:Polysaccharide-Lyases / Q000494:pharmacology
D019763:Heparin Lyase; D006497:Heparan Sulfate; D010978:Platelet Factor 4; D011133:Polysaccharide-Lyases