Clip-domain serine proteases as immune factors in insect hemolymph.
Clip-domain serine proteases as immune factors in insect hemolymph.
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DOI：
10.1016/j.cois.2015.09.003
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发表时间：
2015-10-01
影响因子：
5.3
通讯作者：
Jiang H
中科院分区：
文献类型：
--
作者：
Kanost MR;Jiang H
Clip蛋白酶是存在于昆虫和其他节肢动物血淋巴中的一种非消化性丝氨酸蛋白酶。它们由一个或多个氨基末端片段结构域和一个连接序列和一个羧基末端S1a家族丝氨酸蛋白酶结构域组成。CLIP蛋白水解酶基因已进化为四个分支(CLIPA、CLIPB、CLIPC、CLIPD)，每个分支都以多基因家族的形式存在于昆虫基因组中。Clip蛋白酶在血淋巴天然免疫反应中的作用。其中包括细胞因子Spätzle的蛋白水解性激活，以形成活性的Toll配体，从而合成抗菌肽，以及黑化反应所需的酚氧化酶原的特异性激活。CLIP蛋白水解酶在级联途径中发挥作用。在已经描述的免疫途径中，微生物表面分子刺激启动的模块化丝氨酸蛋白酶的激活，然后激活CLIPC，进而激活CLIPB。然后，活性CLIPB裂解并激活效应分子(前列腺素或酚氧化酶原)。ClipA蛋白是一种假蛋白水解酶，缺乏蛋白水解性，但有些蛋白可以调节其他Clip蛋白的活性，形成高相对分子质量的免疫复合体。目前，一些CLIP酶的三维结构可用于这些免疫因子的结构-功能分析，揭示了可能作用于特定激活或免疫复合体形成的结构特征。大多数CLIP酶的功能是未知的，即使在研究得很好的昆虫物种中也是如此。很可能还没有发现更多由CLIP蛋白酶激活并参与免疫的蛋白质。
CLIP proteases are non-digestive serine proteases present in hemolymph of insects and other arthropods. They are composed of one or more amino-terminal clip domains followed by a linker sequence and a carboxyl-terminal S1A family serine protease domain. The genes for CLIP proteases have evolved as four clades (CLIPA, CLIPB, CLIPC, CLIPD), each present as multigene families in insect genomes. CLIP proteases in hemolymph function in innate immune responses. These include proteolytic activation of the cytokine Spätzle, to form an active Toll ligand leading to synthesis of antimicrobial peptides, and specific activation of prophenoloxidase, required for the melanization response. CLIP proteases act in cascade pathways. In the immune pathways that have been characterized, microbial surface molecules stimulate activation of an initiating modular serine protease, which then activates a CLIPC, which in turn activates a CLIPB. The active CLIPB then cleaves and activates an effector molecule (proSpätzle or prophenoloxidase). CLIPA proteins are pseudoproteases, lacking proteolytic activity, but some can function as regulators of the activity of other CLIP proteases and form high molecular weight immune complexes. A few three dimensional structures for CLIP proteases are now available for structure-function analysis of these immune factors, revealing structural features that may act in specific activation or in formation of immune complexes. The functions of most CLIP proteases are unknown, even in well studied insect species. It is very likely that additional proteins activated by CLIP proteases and acting in immunity remain to be discovered.