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硫酸乙酰肝素组与细胞功能调控:结构、功能及挑战

The heparanome and regulation of cell function: structures, functions and challenges.

作者信息

Ori Alessandro, Wilkinson Mark Charles, Fernig David Garth

机构信息

School of Biological Sciences, University of Liverpool, Liverpool L69 7ZB United Kingdom.

出版信息

Front Biosci. 2008 May 1;13:4309-38. doi: 10.2741/3007.

DOI:10.2741/3007
PMID:18508513
Abstract

The cell-extracellular matrix interface is a crowded space whose structure is dependent on macromolecular assemblies that are dynamic in time, molecular composition and location. Signals travel from one cell to another (or to the same cell) by the regulated assembly/disassembly of molecular complexes. These signals can evoke relatively simple biological responses such cell proliferation and migration, but once integrated, they guide cell fate in complex biological phenomena such as embryonic development and organism homeostasis. Heparan sulfate proteoglycans are ubiquitous components of this space and important actors of these processes in all tissue-organized life forms. A key feature of heparan sulfate is its size, 40 nm to 160 nm, which enables it to integrate self-assembling macromolecular structures over substantial length scales. What is the structure of heparan sulfate? Why do we think heparan sulfate is so important? How do we try to explain its activity? What do we know about its interactions? These questions together with a final look to the future are the "menu" of this review.

摘要

细胞与细胞外基质的界面是一个拥挤的空间,其结构取决于在时间、分子组成和位置上动态变化的大分子组装体。信号通过分子复合物的有序组装/解组装从一个细胞传递到另一个细胞(或同一个细胞)。这些信号可引发相对简单的生物学反应,如细胞增殖和迁移,但一旦整合,它们会在胚胎发育和机体稳态等复杂生物学现象中引导细胞命运。硫酸乙酰肝素蛋白聚糖是这个空间中普遍存在的成分,也是所有组织化生命形式中这些过程的重要参与者。硫酸乙酰肝素的一个关键特征是其大小,为40纳米至160纳米,这使其能够在相当长的长度尺度上整合自组装大分子结构。硫酸乙酰肝素的结构是怎样的?为什么我们认为硫酸乙酰肝素如此重要?我们如何试图解释其活性?我们对其相互作用了解多少?这些问题以及对未来的最后展望构成了本综述的“菜单”。

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