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肝素/硫酸乙酰肝素与蛋白质的相互作用:结构因素与实验方法评估

Interactions of heparin/heparan sulfate with proteins: appraisal of structural factors and experimental approaches.

作者信息

Powell Andrew K, Yates Edwin A, Fernig David G, Turnbull Jeremy E

机构信息

School of Biological Sciences, Biosciences Building, University of Liverpool, Crown Street, Liverpool, L69 7ZB, United Kingdom.

出版信息

Glycobiology. 2004 Apr;14(4):17R-30R. doi: 10.1093/glycob/cwh051. Epub 2004 Jan 12.

DOI:10.1093/glycob/cwh051
PMID:14718374
Abstract

Over the past decade, the glycosaminoglycans heparin and heparan sulfate have been shown to bind and regulate the activities of many proteins. Established techniques have provided both qualitative and quantitative information regarding these interactions, leading to a general view that proteins bind with a variety of affinities to particular sequences within heparin or heparan sulfate chains. The mechanism by which heparan sulfate regulates the activity of proteins through such interactions has, however, proved more elusive. We survey some relevant details of the structural characteristics of heparin/heparan sulfate and the approaches used to investigate their interactions with proteins. For the latter, the interactions of heparin/heparan sulfate with fibroblast growth factors and their receptors will be emphasized, because these proteins have been the subject of many studies. We reflect on the information that various techniques have provided, points regarding their use, and some relevant theoretical considerations regarding the study of protein-heparin/heparan sulfate interactions. A perspective of new and developing approaches, which may aid advances in this field, is also provided.

摘要

在过去十年中,糖胺聚糖肝素和硫酸乙酰肝素已被证明能结合并调节多种蛋白质的活性。现有技术已提供了有关这些相互作用的定性和定量信息,从而形成了一种普遍观点,即蛋白质以多种亲和力与肝素或硫酸乙酰肝素链内的特定序列结合。然而,硫酸乙酰肝素通过此类相互作用调节蛋白质活性的机制却更难捉摸。我们概述了肝素/硫酸乙酰肝素结构特征的一些相关细节以及用于研究它们与蛋白质相互作用的方法。对于后者,将重点介绍肝素/硫酸乙酰肝素与成纤维细胞生长因子及其受体的相互作用,因为这些蛋白质一直是许多研究的主题。我们思考了各种技术所提供的信息、它们的使用要点以及有关蛋白质 - 肝素/硫酸乙酰肝素相互作用研究的一些相关理论考量。还提供了一个关于可能有助于该领域进展的新的和正在发展的方法的展望。

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