A heparin-binding synthetic peptide of heparin/heparan sulfate-interacting protein modulates blood coagulation activities.
We have previously identified and characterized a heparin-binding cell surface protein (heparin/heparan sulfate-interacting protein, or HIP) present on epithelial and endothelial cells. A synthetic peptide mimicking a heparin-binding domain of HIP is now shown to bind a small subset of heparin molecules with high affinity and, therefore, presumably recognizes a specific structural motif in the heparin molecule. Further analyses revealed that the heparin molecules exhibiting a high affinity for the HIP peptide also show an extremely high affinity for antithrombin III (AT-III), a cofactor required for heparin's anticoagulant activity. The HIP peptide was shown to compete with AT-III for binding to heparin and to neutralize the anticoagulant activity of heparin in blood plasma assays. Furthermore, the heparin subfraction that binds to the HIP peptide with high affinity exhibits an extremely high anticoagulant activity. We conclude that although the HIP peptide shows no sequence similarity with AT-III, the two proteins recognize the same or similar structural motifs in heparin.
Liu
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Department of Biochemistry and Molecular Biology, University of Texas M.D. Anderson Cancer Center, Houston 77030, USA.
Zhou
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F
Höök
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Carson
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D000595:Amino Acid Sequence; D000990:Antithrombin III / Q000378:metabolism; D001665:Binding Sites; D001777:Blood Coagulation; D001779:Blood Coagulation Factors; D002352:Carrier Proteins / Q000737:chemistry* / Q000378:metabolism / Q000494:pharmacology; D002478:Cells, Cultured; D002846:Chromatography, Affinity; D015951:Factor Xa / Q000494:pharmacology; D005260:Female; D006493:Heparin / Q000378:metabolism*; D006497:Heparan Sulfate / Q000378:metabolism*; D006801:Humans; D008969:Molecular Sequence Data; D009844:Oligosaccharides / Q000032:analysis / Q000737:chemistry; D010455:Peptides / Q000138:chemical synthesis / Q000737:chemistry / Q000378:metabolism* / Q000494:pharmacology; D011485:Protein Binding; D016601:RNA-Binding Proteins; D012269:Ribosomal Proteins; D013917:Thrombin / Q000378:metabolism / Q000494:pharmacology; D014599:Uterus / Q000378:metabolism
D000990:Antithrombin III; D001779:Blood Coagulation Factors; D002352:Carrier Proteins; D015951:Factor Xa; D006493:Heparin; D006497:Heparan Sulfate; D009844:Oligosaccharides; D010455:Peptides; D016601:RNA-Binding Proteins; D012269:Ribosomal Proteins; D013917:Thrombin; C104946:RPL29 protein, human