Residues on both faces of the first immunoglobulin fold contribute to hemophilic binding sites of PECAM-1/CD31
Residues on both faces of the first immunoglobulin fold contribute to hemophilic binding sites of PECAM-1/CD31
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DOI：
10.1074/jbc.272.33.20555
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发表时间：
1997-08-15
影响因子：
4.8
通讯作者：
Simmons, DL
中科院分区：
文献类型：
--
作者：
Newton, JP;Buckley, CD;Simmons, DL
CD31 （PECAM-1）是免疫球蛋白超家族的一员，其胞外结构域由6个免疫球蛋白样结构域组成。它广泛表达于内皮细胞、血小板、约50%的淋巴细胞和髓系细胞。CD31已被证明参与内皮间粘附和白细胞内皮相互作用，特别是在转运过程中，CD31介导的粘附是复杂的，因为CD31能够介导血友病和多种异源性粘附相互作用。在这里，我们表明CD31的nh2末端（膜远端）免疫球蛋白结构域是必要的，但不足以支持稳定的血友病粘附。通过对26个单点突变的分析，确定了该区域内形成结合位点的关键残基，这是迄今为止对免疫球蛋白超家族成员之间完全血友病相互作用的最系统的分析。这揭示了五个影响血友病结合的突变，独特的是，相关残基暴露在免疫球蛋白折叠的两面，这使我们提出了CD31血友病粘附的新机制。
CD31 (PECAM-1) is a member of the immunoglobulin superfamily whose extracellular domain is comprised of six immunoglobulin-like domains. It is widely expressed on endothelium, platelets, around 50% of lymphocytes, and cells of myeloid lineage. CD31 has been shown to be involved in interendothelial adhesion and leukocyte endothelial interactions, particularly during transmigration, CD31-mediated adhesion is complex, because CD31 is capable of mediating both hemophilic and multiple heterophilic adhesive interactions, Here we show that the NH2-terminal (membrane-distal) immunoglobulin domain of CD31 is necessary but not sufficient to support stable hemophilic adhesion, Key residues forming the binding site within this domain have been identified by analysis of 26 single point mutations, representing the most systematic analysis of a fully hemophilic interaction between immunoglobulin superfamily family members to date. This revealed five mutations that affect hemophilic binding, Uniquely, the residues involved are exposed on both faces of the immunoglobulin fold, leading us to propose a novel mechanism for CD31 hemophilic adhesion.