A heparin-binding synthetic peptide of heparin/heparan sulfate-interacting protein modulates blood coagulation activities
A heparin-binding synthetic peptide of heparin/heparan sulfate-interacting protein modulates blood coagulation activities
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DOI：
10.1073/pnas.94.5.1739
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发表时间：
1997-03-04
影响因子：
11.1
通讯作者：
Carson, DD
中科院分区：
文献类型：
--
作者：
Liu, SC;Zhou, FY;Carson, DD
我们已经鉴定并鉴定了一种存在于上皮细胞和内皮细胞上的肝素结合细胞表面蛋白(肝素/硫酸肝素相互作用蛋白，HIP)。模拟HIP的肝素结合结构域的合成肽现在被证明以高亲和力结合一小部分肝素分子，因此推测识别肝素分子中的特定结构基序，进一步的分析发现显示高亲和力的肝素分子也显示出极高的亲和力，抗凝血酶III(AT-III)是肝素抗凝活性所需的辅助因子，HIP肽被证明与AT-III竞争与肝素结合，并在血浆分析中中和肝素的抗凝活性，此外，与HIP肽结合的肝素亚组份具有极高的抗凝血活性。我们的结论是，虽然HIP肽与AT-III没有序列相似性，但这两种蛋白质识别肝素中相同或相似的结构基序。
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.