ArticleBMC evolutionary biology2011
Evolutionary and functional insights into Leishmania META1: evidence for lateral gene transfer and a role for META1 in secretion.
Article in BMC evolutionary biology, 2011. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 9 papers.
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9 citing papers in PubMed, 10 citations in OpenAlex.
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- Identification of positive and negative regulators in the stepwise developmental progression towards infectivity in Trypanosoma brucei.Scientific reports · 2021Article
- Molecular and antigenic characterization of Trypanosoma cruzi TolT proteins.PLoS neglected tropical diseases · 2019Article
- Article
- Simultaneous transcriptional profiling of Leishmania major and its murine macrophage host cell reveals insights into host-pathogen interactions.BMC genomics · 2015Article
- Transcriptomic profiling of gene expression and RNA processing during Leishmania major differentiation.Nucleic acids research · 2015Article
- Genome evolution in trypanosomatid parasites.Parasitology · 2015Review
- A Novel Trypanosoma cruzi Protein Associated to the Flagellar Pocket of Replicative Stages and Involved in Parasite Growth.PloS one · 2015Article
- Structural insights into the substrate specificity of a 6-phospho-β-glucosidase BglA-2 from Streptococcus pneumoniae TIGR4.The Journal of biological chemistry · 2013Article
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Authors and funding
5 authors at 3 institutions in 4 countries.
Funding
Abstract
backgroundLeishmania META1 has for long been a candidate molecule for involvement in virulence: META1 transcript and protein are up-regulated in metacyclic Leishmania. Yet, how META1 contributes to virulence remains unclear. We sought insights into the possible functions of META1 by studying its evolutionary origins.
resultsUsing multiple criteria including sequence similarity, nucleotide composition, phylogenetic analysis and selection pressure on gene sequence, we present evidence that META1 originated in trypanosomatids as a result of a lateral gene transfer of a bacterial heat-inducible protein, HslJ. Furthermore, within the Leishmania genome, META1 sequence is under negative selection pressure against change/substitution. Using homology modeling of Leishmania META1 based on solved NMR structure of HslJ, we show that META1 and HslJ share a similar structural fold. The best hit for other proteins with similar fold is MxiM, a protein involved in the type III secretion system in Shigella. The striking structural similarity shared by META1, HslJ and MxiM suggests a possibility of shared functions. Upon structural superposition with MxiM, we have observed a putative hydrophobic cavity in META1. Mutagenesis of select hydrophobic residues in this cavity affects the secretion of the secreted acid phosphatase (SAP), indicating META1's involvement in secretory processes in Leishmania.
conclusionsOverall, this work uses an evolutionary biology approach, 3D-modeling and site-directed mutagenesis to arrive at new insights into functions of Leishmania META1.
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