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).

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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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