Evolutionary duplication of the leishmanial adaptor protein α-SNAP plays a role in its pathogenicity.

IF 4 2区 生物学 Q2 BIOCHEMISTRY & MOLECULAR BIOLOGY
Shankari Prasad Datta, Chinmoy Sankar Dey
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引用次数: 0

Abstract

Essential-gene duplication during evolution promotes specialized functions beyond the typical role. Our in-silico study unveiled two α-SNAP paralogs in Leishmania, a crucial component that, along with NSF, triggers disassembly of the cis-SNARE complex, formed during vesicle fusion with target membranes. While multiple α-SNAPs are common in many flagellated protists, including the trypanosomatids, they are unusual among other eukaryotes. This study explores the evolutionary and functional relevance of α-SNAP gene duplication in Leishmania donovani, emphasizing both subfunctionalization and neofunctionalization. We discovered that Leishmania donovani α-SNAP (Ldα-SNAP) genes are transcribed in promastigote and amastigote stages, indicating they are not pseudogenes. Although the two paralogs share essential residues and structural features, only Ldα-SNAP1660 (Ldα-SNAP1) can effectively substitute the function of its yeast counterpart, while Ldα-SNAP3040 (Ldα-SNAP2) cannot. This functional difference is attributed to a replacement of alanine with phosphorylatable-serine in Ldα-SNAP1 during evolution from the most common ancestral ortholog. This modification is rarely observed in corresponding orthologs of other trypanosomatids. Incidentally, Ldα-SNAP paralogs exhibit differential localization in the ER and flagellar pocket. However, both paralogs, either actively or passively, regulate the secretion of exosomes and PM blebs, containing the virulence protein GP63. This indicates functional division and their indirect participation in host's macrophage inactivation. Moreover, a small fraction of Ldα-SNAP1's presence in flagellum hints at a potential role in sensing environmental cues and aiding parasite's attachment to the sandfly's hindgut. Our findings underscore that duplicated Ldα-SNAPs have retained ancestral functions through subfunctionalization, and subsequently, they acquired parasite-specific neofunction(s) through accumulation of natural mutation(s).

利什曼适应蛋白α-SNAP的进化复制在其致病性中起作用。
在进化过程中,必要基因的复制促进了超越典型作用的特殊功能。我们的计算机研究揭示了利什曼原虫的两个α-SNAP类似物,这是一个关键的成分,与NSF一起,触发在囊泡与靶膜融合过程中形成的顺式snare复合物的分解。虽然多个α- snap在许多鞭毛原生生物(包括锥虫)中很常见,但在其他真核生物中并不常见。本研究探讨了多诺瓦利什曼原虫α-SNAP基因重复的进化和功能相关性,强调了亚功能化和新功能化。我们发现,多诺瓦利什曼原虫α-SNAP (Ldα-SNAP)基因在promastigote和amastigote阶段都有转录,表明它们不是假基因。虽然这两个相似物具有相同的基本残基和结构特征,但只有Ldα-SNAP1660 (Ldα-SNAP1)可以有效替代其酵母菌对应物的功能,而Ldα-SNAP3040 (Ldα-SNAP2)则不能。这种功能差异归因于在从最常见的祖先同源物进化过程中,Ldα-SNAP1中的丙氨酸被磷酸化丝氨酸取代。这种变异在其他锥虫的相应同源物中很少观察到。顺便说一句,Ldα-SNAP类似物在内质网和鞭毛袋中表现出不同的定位。然而,这两种类似物,无论是主动还是被动,都调节外泌体和PM泡的分泌,其中含有毒力蛋白GP63。这表明功能分裂及其间接参与宿主巨噬细胞失活。此外,鞭毛中存在的一小部分Ldα-SNAP1暗示了它在感知环境信号和帮助寄生虫附着在白蛉后肠中的潜在作用。我们的研究结果强调,重复的ld α- snap通过亚功能化保留了祖先的功能,随后,它们通过自然突变的积累获得了寄生虫特异性的新功能。
本文章由计算机程序翻译,如有差异,请以英文原文为准。
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来源期刊
Journal of Biological Chemistry
Journal of Biological Chemistry Biochemistry, Genetics and Molecular Biology-Biochemistry
自引率
4.20%
发文量
1233
期刊介绍: The Journal of Biological Chemistry welcomes high-quality science that seeks to elucidate the molecular and cellular basis of biological processes. Papers published in JBC can therefore fall under the umbrellas of not only biological chemistry, chemical biology, or biochemistry, but also allied disciplines such as biophysics, systems biology, RNA biology, immunology, microbiology, neurobiology, epigenetics, computational biology, ’omics, and many more. The outcome of our focus on papers that contribute novel and important mechanistic insights, rather than on a particular topic area, is that JBC is truly a melting pot for scientists across disciplines. In addition, JBC welcomes papers that describe methods that will help scientists push their biochemical inquiries forward and resources that will be of use to the research community.
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