Kibria K M Kaderi, Hossain Mohammad Uzzal, Oany Arafat Rahman, Ahmad Shah Adil Ishtiyaq
Department of Biotechnology and Genetic Engineering, Mawlana Bhashani Science and Technology University, Santosh, Tangail, 1902, Bangladesh.
Parasitol Res. 2016 Jun;115(6):2191-202. doi: 10.1007/s00436-016-4961-1. Epub 2016 Feb 27.
The phylum Apicomplexa includes a large group of early branching eukaryotes having significant medical and economical importance. The molecular machinery responsible for protein trafficking is poorly understood in these apicomplexans. One of the most important proteins involved in clathrin-mediated protein trafficking is Epsin, which contains ENTH domain, a conserved domain crucial for membrane bending leading to vesicle formation. We undertook homology searching and phylogenetic analyses to produce a rigorously annotated set of Epsin homologs retrieved from diverse apicomplexan genomes. Genomic and phylogenetic comparisons revealed that apicomplexans contain unusual Epsin homologs that are distinct from those observed in mammals and yeast. Although there are four Epsin genes in mammalian system and five in the yeast genome, apicomplexan parasites consist only a single Epsin gene. The apicomplexan Epsin contains the conserved ENTH domain consisting of phosphoinositide (PtdIns)-binding sites which indicate about their functional significance in the formation of vesicles; however, the absence of ubiquitin-interacting motif (UIM) suggests a possible different mechanism for protein trafficking. The existence of dileucine motif in Plasmodium, Cryptosporidum parvum and Eimeria tenella Epsins might solve their functionality while lacking a lot of conserved motifs as this motif is known to interact with different adaptor protein complexes (AP1, AP2 and AP3). Other Epsin homologs are also shown to have different peptide motifs reported for possible interaction with α-ear appendage, γ-ear appendage and EH domain present in different adaptors. Bioinformatic and phylogenetic analyses suggest that the apicomplexan Epsins have unusual functionality from that of the mammalian Epsins. This detailed study may greatly facilitate future molecular cell biological investigation for the role of Epsins in these parasites.
顶复门包含一大类早期分支的真核生物，具有重要的医学和经济意义。在这些顶复门生物中，负责蛋白质运输的分子机制尚不清楚。网格蛋白介导的蛋白质运输中最重要的蛋白质之一是Epsin，它含有ENTH结构域，这是一个对导致囊泡形成的膜弯曲至关重要的保守结构域。我们进行了同源性搜索和系统发育分析，以生成一组从不同顶复门基因组中检索到的经过严格注释的Epsin同源物。基因组和系统发育比较表明，顶复门生物含有不寻常的Epsin同源物，与在哺乳动物和酵母中观察到的不同。虽然哺乳动物系统中有四个Epsin基因，酵母基因组中有五个，但顶复门寄生虫仅由一个Epsin基因组成。顶复门Epsin含有由磷酸肌醇（PtdIns）结合位点组成的保守ENTH结构域，这表明它们在囊泡形成中具有功能意义；然而，泛素相互作用基序（UIM）的缺失表明蛋白质运输可能存在不同的机制。疟原虫、微小隐孢子虫和柔嫩艾美耳球虫的Epsin中双亮氨酸基序的存在可能解决它们的功能问题，同时缺乏许多保守基序，因为已知该基序与不同的衔接蛋白复合物（AP1、AP2和AP3）相互作用。其他Epsin同源物也显示出不同的肽基序，据报道可能与不同衔接蛋白中存在的α-耳附属物、γ-耳附属物和EH结构域相互作用。生物信息学和系统发育分析表明，顶复门Epsin具有与哺乳动物Epsin不同的功能。这项详细的研究可能会极大地促进未来对Epsin在这些寄生虫中的作用的分子细胞生物学研究。
