ADAMTS Proteins: Concepts, Challenges, and Prospects
ADAMTS Proteins: Concepts, Challenges, and Prospects
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DOI：
10.1007/978-1-4939-9698-8_1
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发表时间：
2020-01-01
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影响因子：
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通讯作者：
Apte, Suneel S.
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作者：
Apte, Suneel S.
ADAMTS 超家族包含分泌型金属蛋白酶（ADAMTS 蛋白酶）以及结构相关但缺乏催化活性的分泌型糖蛋白（ADAMTS 样蛋白）。这两个家族的成员在胚胎发育过程中参与不同的形态发生过程，并在成人中参与结缔组织的维持和止血。几种 ADAMTS 蛋白与遗传性和后天性人类和动物疾病密切相关。尽管这些指标具有深远的生物学和医学重要性，但对其分子结构、底物、生物途径和生化机制的详细了解受到独特的内在特征的极大限制，这导致了一些技术挑战。作为一个群体，它们比其他分泌型蛋白酶更大、修饰更严重且更难纯化。此外，个别成员的特质值得进一步调查，但可能会使分析变得复杂。在此，根据过去二十年积累的知识，讨论了 ADAMTS 研究中的一些关键概念、挑战和前景。本卷《分子生物学方法》中的各个章节提供了克服这些挑战的实用解决方案。由于蛋白酶的生物学实际上是其底物的生物学，因此非常重视重组 ADAMTS 蛋白的纯化、其底物的鉴定以及其蛋白水解活性的测定。
The ADAMTS superfamily comprises secreted metalloproteases (ADAMTS proteases) as well as structurally related secreted glycoproteins that lack catalytic activity (ADAMTS-like proteins). Members of both families participate in diverse morphogenetic processes during embryonic development, and connective tissue maintenance and hemostasis in the adult. Several ADAMTS proteins are heavily implicated in genetic and acquired human and animal disorders. Despite these indicators of a profound biological and medical importance, detailed knowledge about their molecular structures, substrates, biological pathways, and biochemical mechanisms is significantly limited by unique intrinsic characteristics, which have led to several technical challenges. As a group, they are larger, more heavily modified, and harder to purify than other secreted proteases. In addition, idiosyncratic aspects of individual members are deserving of further investigation but can complicate their analysis. Here, some of the key concepts, challenges, and prospects in ADAMTS research are discussed in the context of the knowledge accumulated over the past two decades. Individual chapters in this volume of Methods in Molecular Biology provide practical solutions for surmounting these challenges. Since the biology of a protease is actually the biology of its substrates, there is considerable emphasis on purification of recombinant ADAMTS proteins, identification of their substrates and assays for their proteolytic activity.