Glycosaminoglycan specificity of a heparin-binding peptide.
Glycosaminoglycans are complex sulfated polysaccharides with a diverse range of biological functions. Three glycosaminoglycan standards--chondroitin sulfate, dermatan sulfate and heparin--were characterized during this study. The interaction of the heparin binding site of protein C inhibitor, represented by the peptide sequence 264-283, in solution with the above glycosaminoglycan standards was studied. Circular dichroism spectroscopy was used to determine the dominant secondary structure induced in the peptide upon binding the relevant glycosaminoglycans. The various glycosaminoglycans induced different secondary structures. The level of induced secondary structure by dermatan sulfate and heparin was approximately twice that induced by chondroitin sulfate. For chondroitin sulfate and heparin, alpha-helix was the dominant ordered secondary structure, whereas for dermatan sulfate the beta-strand conformation dominated. The order of secondary structure induction of the protein C inhibitor peptide by the glycosaminoglycans paralleled the reported biological activities of these glycosaminoglycans for mediation of the biological activity in the intact protein. The strength of the interaction of dermatan sulfate and heparin with the protein C inhibitor peptide was measured by determining the concentration of salt required to inhibit 50% of the interaction. The values determined were 0.1 and 0.3 M salt for dermatan sulfate and heparin, respectively. These results show that different glycosaminoglycans can support different secondary structures in the protein C inhibitor peptide.
Taylor
G J
GJ
Massey University, Palmerston North, New Zealand.
Yorke
S C
SC
Harding
D R
DR
D000595:Amino Acid Sequence; D001665:Binding Sites; D002809:Chondroitin Sulfates / Q000378:metabolism; D002942:Circular Dichroism; D003871:Dermatan Sulfate / Q000378:metabolism; D006025:Glycosaminoglycans / Q000378:metabolism*; D006493:Heparin / Q000378:metabolism*; D008969:Molecular Sequence Data; D018046:Protein C Inhibitor / Q000737:chemistry* / Q000378:metabolism*; D017433:Protein Structure, Secondary
D006025:Glycosaminoglycans; D018046:Protein C Inhibitor; D003871:Dermatan Sulfate; D006493:Heparin; D002809:Chondroitin Sulfates