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组织凝集素感知糖作为生化信使:血管生物学中的糖码作用。

Sensing Glycans as Biochemical Messages by Tissue Lectins: The Sugar Code at Work in Vascular Biology.

机构信息

Institut für Physiologische Chemie, Tierärztliche Fakultät, Ludwig-Maximilians-Universität München, München, Germany.

出版信息

Thromb Haemost. 2019 Apr;119(4):517-533. doi: 10.1055/s-0038-1676968. Epub 2019 Jan 8.

Abstract

Although a plethora of players has already been revealed to be engaged in the haemostatic system, a fundamental consideration of the molecular nature of information coding can give further explorations of the mechanisms of blood clotting, platelet functionality and vascular trafficking direction. By any measures, looking at ranges of occurrence and of potential for structural versatility, at strategic positioning to influence protein and cell sociology as well as at dynamics of processing and restructuring for phenotypic variability, using sugars as an alphabet of life for generating the glycan part of glycoconjugates is a success story. The handiwork by the complex system for glycan biosynthesis renders biochemical messages of exceptionally high coding capacity available. They are read and translated into cellular effects by receptors termed lectins. The different levels of regulation on both sides, that is, glycan and lectin, establish an intriguingly fine-tuned capacity for functional pairing. The emerging insights into the highly branched routes of glycosylation, into lectin structures up to complete characterization in solution and the shape of lectin networks, first obtained for the three selectins, now extended to considering many other C-type lectins, galectins and siglecs, as well as into intra- and inter-family cross-talk and cooperations are sure to push boundaries in our understanding of the molecular basis of haemostasis.

摘要

尽管已经有大量的参与者被揭示参与了止血系统,但对分子信息编码本质的基本考虑可以为进一步探索凝血、血小板功能和血管运输的机制提供方向。无论从哪个角度来看,考虑到发生的范围和结构多功能性的潜力、在影响蛋白质和细胞社会学以及处理和重构表型变异性的动力学方面的战略定位,将糖作为生命的字母表用于生成糖缀合物的聚糖部分是一个成功的故事。复杂的聚糖生物合成系统的杰作使得具有极高编码能力的生化信息得以实现。它们被称为凝集素的受体读取和翻译成细胞效应。糖和凝集素双方的不同调节水平,建立了一种引人入胜的精细功能配对能力。在高度分支的糖基化途径、在溶液中完整表征的凝集素结构以及凝集素网络的形状方面的新见解,最初是在三种选择素中获得的,现在扩展到考虑许多其他 C 型凝集素、半乳糖凝集素和 Siglec 以及家族内和家族间的串扰和合作,肯定会推动我们对止血分子基础的理解的界限。

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