Three noncontiguous peptides comprise binding sites on high-molecular-weight kininogen to neutrophils
Three noncontiguous peptides comprise binding sites on high-molecular-weight kininogen to neutrophils
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DOI：
10.1152/ajpheart.1998.275.1.h145
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发表时间：
1998-07-01
影响因子：
4.8
通讯作者：
Colman, RW
中科院分区：
文献类型：
--
作者：
Khan, MMH;Kunapuli, SP;Colman, RW
高分子量激肽原（HX）与中性粒细胞（多形核白细胞，PMN）的结合是人血浆激肽释放酶刺激聚集和脱粒以及纤维蛋白原从该细胞表面置换所必需的。HK的假定受体是白细胞整合素α（M）β（2），HK的结构域3（D3）和5（D5）形成其结合位点。为了进一步定位HK上PMN的结合位点，我们使用D3重组外显子产物并设计来自D3和D5的肽。在D3中，来自外显子7产物的七肽Leu（271）-Ala（277）和来自外显子9产物的肽Cys（333）-Cys（352）可以抑制激肽原与PMN的结合。D5富含组氨酸-甘氨酸区的两个连续肽Gly（442）-Lys（458）和Phe（459）-Lys（478）均抑制HK与PMN的结合。因此，这项研究描绘了三个非连续的表面导向的序列HK，其中包括所有或大部分的人PMN的结合位点。
The binding of high-molecular-weight kininogen (HX) to neutrophils (polymorphonuclear leukocytes, PMN) is required for the stimulation of aggregation and degranulation by human plasma kallikrein as well as the displacement of fibrinogen from this cell surface. The putative receptor for HK is the leukocyte integrin alpha(M)beta(2), and domains 3 (D3) and 5 (D5) of HK form its binding site. To further map the binding sites on HK for PMN, we used D3 recombinant exon products and designed peptides from D3 and D5. In D3, a heptapeptide, Leu(271)-Ala(277) from exon 7 product, and a peptide, Cys(333)-Cys(352), from exon 9 product can inhibit binding of kininogen to PMN. Two contiguous peptides from D5 in the histidine-glycine-rich region, Gly(442)-Lys(458) and Phe(459)-Lys(478), each inhibit the binding of HK to PMN. This study has thus delineated three noncontiguous surface-oriented sequences on HK, which together comprise all or most of the binding site for human PMN.