The calpains: modular designs and functional diversity.
The calpains: modular designs and functional diversity.
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DOI：
10.1186/gb-2007-8-6-218
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发表时间：
2007
期刊：
影响因子：
12.3
通讯作者：
Ersfeld K
中科院分区：
文献类型：
--
作者：
Croall DE;Ersfeld K
真核生物钙蛋白酶是一类钙依赖性木瓜蛋白酶样蛋白酶及其非酶类蛋白酶家族，其多种生理功能正开始被充分研究。钙蛋白酶家族是根据广泛研究的普遍存在的脊椎动物酶钙蛋白酶-1（μ-钙蛋白酶）和钙蛋白酶-2（m-钙蛋白酶）的木瓜蛋白酶样巯基蛋白酶活性的钙依赖性而命名的。这些酶的催化核心结构域的序列相关的蛋白质包括在这个古老的和不同的真核蛋白质家族。钙蛋白酶是高度模块化组织的例子，在保守的核心两侧有几种氨基末端或羧基末端模块。收购五EF手模块参与钙结合（和形成异源二聚体的一些钙蛋白酶）似乎是一个相对较晚的事件钙蛋白酶的演变。在整个家族中发现了几种结合钙和与膜/磷脂结合的替代机制。该基因家族在哺乳动物、锥虫和纤毛虫中扩展，例如在四膜虫中有多达26个成员;与此形成鲜明对比的是，在许多其他原生动物和植物中只有一个钙蛋白酶基因。钙蛋白酶的多种异构体及其多种剪接变体使该家族的讨论和分析复杂化，并挑战研究人员确定钙蛋白酶基因序列，蛋白质异构体及其独特或重叠功能之间的关系。在哺乳动物和植物中，很明显钙蛋白酶在发育中起着至关重要的作用。越来越多的证据表明，普遍存在的钙蛋白酶参与多种信号转导途径，并在重要的细胞生命和死亡过程中发挥作用。与相对混杂的降解蛋白酶相比，钙蛋白酶仅切割有限的蛋白质底物，并使用复杂的底物识别机制，涉及靶蛋白的一级和二级结构特征。蛋白水解活性钙蛋白酶和那些缺乏关键催化残基的详细生理意义需要进一步研究。
The eukaryotic calpains are a family of calcium-dependent papain-like proteases and their non-enzymatic relatives whose varied physiological functions are beginning to be fully explored. The calpain family is named for the calcium dependence of the papain-like, thiol protease activity of the well-studied ubiquitous vertebrate enzymes calpain-1 (μ-calpain) and calpain-2 (m-calpain). Proteins showing sequence relatedness to the catalytic core domains of these enzymes are included in this ancient and diverse eukaryotic protein family. Calpains are examples of highly modular organization, with several varieties of amino-terminal or carboxy-terminal modules flanking a conserved core. Acquisition of the penta-EF-hand module involved in calcium binding (and the formation of heterodimers for some calpains) seems to be a relatively late event in calpain evolution. Several alternative mechanisms for binding calcium and associating with membranes/phospholipids are found throughout the family. The gene family is expanded in mammals, trypanosomes and ciliates, with up to 26 members in Tetrahymena, for example; in striking contrast to this, only a single calpain gene is present in many other protozoa and in plants. The many isoforms of calpain and their multiple splice variants complicate the discussion and analysis of the family, and challenge researchers to ascertain the relationships between calpain gene sequences, protein isoforms and their distinct or overlapping functions. In mammals and plants it is clear that a calpain plays an essential role in development. There is increasing evidence that ubiquitous calpains participate in a variety of signal transduction pathways and function in important cellular processes of life and death. In contrast to relatively promiscuous degradative proteases, calpains cleave only a restricted set of protein substrates and use complex substrate-recognition mechanisms, involving primary and secondary structural features of target proteins. The detailed physiological significance of both proteolytically active calpains and those lacking key catalytic residues requires further study.
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影响因子：
7.8
作者：
Demarchi, Francesca;Bertoli, Cosetta;Copetti, Tamara;Tanida, Isei;Brancolini, Claudio;Eskelinen, Eeva-Liisa;Schneider, Claudio
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影响因子：
--
作者：
Dutt P;Croall DE;Arthur JS;Veyra TD;Williams K;Elce JS;Greer PA
通讯作者：
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