Ligand heterogeneity of the cysteine protease binding protein family in the parasitic protist Entamoeba histolytica
Ligand heterogeneity of the cysteine protease binding protein family in the parasitic protist Entamoeba histolytica
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DOI：
10.1016/j.ijpara.2014.04.008
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发表时间：
2014-08-01
影响因子：
4
通讯作者：
Nozaki, Tomoyoshi
中科院分区：
文献类型：
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作者：
Marumo, Konomi;Nakada-Tsukui, Kumiko;Nozaki, Tomoyoshi
溶酶体可溶性蛋白质通过内质网和/或高尔基体中的特定受体靶向内体和溶酶体。肠道原生动物寄生虫溶组织内阿米巴具有一类新型溶酶体靶向受体，称为半胱氨酸蛋白酶结合蛋白家族（CPBF）。在11个CPBF（CPBF1-11）中，CPBF1、CPBF6和CPBF8这三个成员的配体先前被证明分别是半胱氨酸蛋白酶、α-和γ-淀粉酶、以及β-己糖胺酶和溶菌酶。为了进一步了解CPBF配体的异质性，我们尝试通过免疫沉淀和质谱分析来分离和鉴定CPBF其他成员的配体，即CPBF2、3、4、5、7、9、10和11。我们发现 CPBF2 和 CPBF10 与 α-淀粉酶结合，而 CPBF7 与 β-己糖胺酶结合。有趣的是，半胱氨酸蛋白酶仅被 CPBF1 识别，而三种 α-淀粉酶和 β-氨基己糖苷酶分别被 3 个和 2 个 CPBF 冗余识别。生物信息学分析和系统发育重建表明，每个CPBF包含6个前肽酶羧基端结构域，且结构域结构在CPBF之间进化保守。总而言之，具有独特且保守的结构域组织的 CPBF 对半胱氨酸蛋白酶和碳水化合物降解酶具有显着的配体异质性。需要进一步的结构研究来阐明配体特异性的结构基础。 (C) 2014 年作者。由 Elsevier Ltd. 代表澳大利亚寄生虫学协会出版。这是一篇遵循 CC BY-NC-SA 许可 (http://creativecommons.org/licenses/by-nc-sa/3.0/) 的开放获取文章。
Lysosomal soluble proteins are targeted to endosomes and lysosomes by specific receptors resident in the endoplasmic reticulum and/or the Golgi apparatus. The enteric protozoan parasite Entamoeba histolytica has a novel class of lysosomal targeting receptors, named the cysteine protease binding protein family (CPBF). Among 11 CPBFs (CPBF1-11), ligands for three members, CPBF1, CPBF6 and CPBF8, were previously shown to be cysteine proteases, alpha- and gamma- amylases, and beta-hexosaminidase and lysozymes, respectively. To further understand the heterogeneity of the ligands of CPBFs, we attempted to isolate and identify the ligands for other members of CPBFs, namely CPBF2, 3, 4, 5, 7, 9, 10 and 11, by immunoprecipitation and mass spectrometric analysis. We found that CPBF2 and CPBF10 bound to alpha-amylases while CPBF7 bound to beta-hexosaminidases. It is intriguing that cysteine protease are exclusively recognised by CPBF1, whereas three alpha-amylases and beta-hexosaminidases are redundantly recognised by three and two CPBFs, respectively. It was shown by bioinformatics analysis and phylogenetic reconstruction that each CPBF contains six prepeptidase carboxyl-terminal domains, and the domain configuration is evolutionarily conserved among CPBFs. Taken together, CPBFs with unique and conserved domain organisation have a remarkable ligand heterogeneity toward cysteine protease and carbohydrate degradation enzymes. Further structural studies are needed to elucidate the structural basis of the ligand specificity. (C) 2014 The Authors. Published by Elsevier Ltd. on behalf of Australian Society for Parasitology Inc. This is an open access article under the CC BY-NC-SA license (http://creativecommons.org/licenses/by-nc-sa/3.0/).