Heparin-protein interactions: From affinity and kinetics to biological roles. Application to an interaction network regulating angiogenesis
Heparin-protein interactions: From affinity and kinetics to biological roles. Application to an interaction network regulating angiogenesis
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DOI：
10.1016/j.matbio.2013.11.001
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发表时间：
2014-04-01
期刊：
影响因子：
6.9
通讯作者：
Ricard-Blum, Sylvie
中科院分区：
文献类型：
--
作者：
Peysselon, Franck;Ricard-Blum, Sylvie
参与多种生物过程的细胞外蛋白质、生长因子、趋化因子、细胞因子、酶、脂蛋白与肝素和/或硫酸肝素在细胞表面和细胞外基质(ECM)中相互作用。本研究的目的是研究肝素-蛋白质相互作用的亲和力和动力学与蛋白质的定位、内在紊乱及其生物学作用之间的关系(S)。大多数蛋白质与肝素的结合比它们的片段亲和力更高，与肝素形成的复合体比与硫酸肝素形成的更稳定。脂蛋白和基质相关蛋白(如生长因子和细胞因子)以非常高的亲和力与肝素结合。配子体相关蛋白与肝素形成暂态复合体。然而，它们与这种糖胺多聚糖结合的亲和力高于有助于细胞外基质组装和组织的核心母体蛋白，也高于与细胞外基质无关的分泌蛋白。蛋白质与肝素的结合率与肝素结合部位的内在紊乱有关。酶抑制活性、蛋白质二聚化、骨骼系统发育和癌症中的途径在功能上与对肝素具有高亲和力或极高亲和力的蛋白质有关(K-D<；100 NM)。除了用于研究分子识别和功能外，动力学和亲和力对于确定网络中相互作用的优先顺序和建立网络模型是必不可少的，正如内皮抑素在内皮细胞表面建立的相互作用网络所讨论的那样，内皮抑素是一种调节血管生成的肝素结合蛋白。(C)2013爱思唯尔B.V.保留所有权利。
Numerous extracellular proteins, growth factors, chemokines, cytokines, enzymes, lipoproteins, involved in a variety of biological processes, interact with heparin and/or heparan sulfate at the cell surface and in the extracellular matrix (ECM). The goal of this study is to investigate the relationship(s) between affinity and kinetics of heparin-protein interactions and the localization of the proteins, their intrinsic disorder and their biological roles. Most proteins bind to heparin with a higher affinity than their fragments and form more stable complexes with heparin than with heparan sulfate. Lipoproteins and matrisome-associated proteins (e.g. growth factors and cytokines) bind to heparin with very high affinity. Matrisome-associated proteins form transient complexes with heparin. However they bind to this glycosaminoglycan with a higher affinity than the proteins of the core matrisome, which contribute to ECM assembly and organization, and than the secreted proteins which are not associated with the ECM. The association rate of proteins with heparin is related to the intrinsic disorder of heparin-binding sites. Enzyme inhibitor activity, protein dimerization, skeletal system development and pathways in cancer are functionally associated with proteins displaying a high or very high affinity for heparin (K-D < 100 nM). Besides their use in investigating molecular recognition and functions, kinetics and affinity are essential to prioritize interactions in networks and to build network models as discussed for the interaction network established at the surface of endothelial cells by endostatin, a heparin-binding protein regulating angiogenesis. (C) 2013 Elsevier B.V. All rights reserved.