THE STRUCTURE AND FUNCTION OF PROTEIN MODULES

THE STRUCTURE AND FUNCTION OF PROTEIN MODULES
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DOI:
10.1098/rstb.1991.0045
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发表时间:
1991-05-29
影响因子:
6.3
通讯作者:
BARON, M
BARON, M
中科院分区:
生物学1区
文献类型:
--
作者:
CAMPBELL, ID;BARON, M

文献摘要

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蛋白质序列分析表明,多细胞生物中的许多蛋白质是通过外显子改组、缺失和复制的过程进化而来的。这些外显子通常对应于自主折叠的蛋白质模块。许多胞外酶都具有这种模块化结构;例如,参与凝血、纤维蛋白溶解和补体的丝氨酸蛋白酶。这些模块的主要作用是通过蛋白质-蛋白质相互作用赋予特异性。由于缺乏此类蛋白质的结构信息,需要一种新的策略来研究蛋白质模块的结构和功能。该策略包括通过蛋白质表达技术生产各个模块,通过高分辨率核磁共振确定其结构,并通过定点诱变和生物测定来定义模块上的功能补丁。简要描述了生长因子模块、纤连蛋白1型模块和补体模块的结构。讨论了各种蛋白质中模块可能的功能作用,包括酶因子 IX 和组织纤溶酶原激活剂。
Analysis of protein sequences shows that many proteins in multicellular organisms have evolved by a process of exon shuffling, deletion and duplication. These exons often correspond to autonomously folding protein modules. Many extracellular enzymes have this modular structure; for example, serine proteases involved in blood-clotting, fibrinolysis and complement. The main role of these modules is to confer specificity by protein-protein interactions. Lack of structural information about such proteins has required a new strategy for studying the structure and function of protein modules. The strategy involves the production of individual modules by protein expression techniques, determination of their structure by high resolution nuclear magnetic resonance and definition of functional patches on the modules by site-directed mutagenesis and biological assays. The structures of the growth factor module, the fibronectin type 1 module and the complement module are briefly described. The possible functional roles of modules in various proteins, including the enzymes factor IX and tissue plasminogen activator, are discussed.