Heparin binding domain of antithrombin III: characterization using a synthetic peptide directed polyclonal antibody.
Heparin binding domain of antithrombin III: characterization using a synthetic peptide directed polyclonal antibody.
复制标题
抗凝血酶 III 的肝素结合域：使用合成肽定向多克隆抗体进行表征。
DOI：
10.1021/bi00490a010
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发表时间：
1990
期刊：
影响因子：
2.9
通讯作者：
Knauer,DJ
中科院分区：
文献类型：
--
作者：
Smith,JW;Dey,N;Knauer,DJ
Department of Developmental and Cell Biology, University of California, Irvine, California 92717 Received April 12, 1990; Revised Manuscript Received May 22, 1990 abstract: Antithrombin III (ATIII) is a plasma-borne serine protease inhibitor thatapparently forms covalent complexes with thrombin. The interaction between ATIII and thrombin is enhanced several thousandfold by the glycosaminoglycan, heparin. Wehave previously proposed that the heparin binding site of ATIII resides within a region extending from amino acid residues 114-156 [Smith, J. W., & Knauer, D. J.(1987) J. Biol. Chem. 262, 11964-11972]. Computer-assisted analysis of this region revealed the presence of a 22 amino acid domain (residues 124-145), part of which shows a strong potentialfor the formation of an amphipathic helix: hydrophobic on one face and highly positively charged on the other. In the presence studies, polyclonal antisera were generated against a synthetic peptide corresponding to residues 124-145 in native human ATIII. Affinity-purified IgGfrom these antisera, as well as monovalent Fab’s derived from them, specifically blocked the binding of heparin to ATIII. Additionally, occupancy of the heparin binding site by these same monovalent and bivalent IgG’s at least partially substituted for heparin, accelerating linkage formation between ATIII and thrombin. These results provide the first immunological evidence that region 124-145 is directly involved in the binding of heparin to ATIII and that an anti-body-induced conformational change within this region can mediate ATIII activation.
