MolEvolvR: A web-app for characterizing proteins using molecular evolution and phylogeny

Burke, Joseph; Chen, Samuel Z; Sosinski, Lo M.; Johnston, J. H.; Ravi, Janani

doi:10.1101/2022.02.18.461833

Cited by 8 publications

(24 citation statements)

References 72 publications

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“…To begin investigating the evolutionary conservation of the L. monocytogenes internalin P (InlP Lm ), we started with an extensive homology search and protein characterization of InlP-like proteins in diverse lineages across the tree of life using MolEvolvR [20] (http://jravilab.org/molevolvr). Most homologs were only present within the genus Listeria .…”

Section: Resultsmentioning

confidence: 99%

“…ivanovii and L. seeligeri as new starting points for our homology search and characterization (using MolEvolvR [20]; see the Methods section). We found several hits in our multi-start search, including proteins that contain transmembrane domains, resembling InlB rather than InlP ().…”

Section: Resultsmentioning

confidence: 99%

“…First, we analysed the InlP amino acid sequence with MolEvolvR [20] to retrieve homologous proteins across evolutionary lineages. MolEvolvR [20] is a powerful new bioinformatic web application to characterize protein families using molecular evolution and phylogeny (http://jravilab.org/molevolvr). The MolEvolvR [20] InlP search returned a list of potential homologs, including those found in Listeria species.…”

Section: Discussionmentioning

confidence: 99%

“…Percentage identity and percentage similarity values for predicted homologs were provided by MolEvolvR [20] (Table S1, available in the online version of this article; https://github.com/jravilab/inlp_listeria). Nucleotide sequences for inlP in L.…”

Section: Methodsmentioning

confidence: 99%

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Novel internalin P homologs in Listeria

et al. 2022

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Listeria monocytogenes (Lm) is a bacterial pathogen that causes listeriosis in immunocompromised individuals, particularly pregnant women. Several virulence factors support the intracellular lifecycle of Lm and facilitate cell-to-cell spread, allowing it to occupy multiple niches within the host and cross-protective barriers, including the placenta. One family of virulence factors, internalins, contributes to Lm pathogenicity by inducing specific uptake and conferring tissue tropism. Over 25 internalins have been identified thus far, but only a few have been extensively studied. Internalins contain leucine-rich repeat (LRR) domains that enable protein-protein interactions, allowing Lm to bind host proteins. Notably, other Listeria species express internalins but cannot colonize human hosts, prompting questions regarding the evolution of internalins within the genus Listeria . Internalin P (InlP) promotes placental colonization through interaction with the host protein afadin. Although prior studies of InlP have begun to elucidate its role in Lm pathogenesis, there remains a lack of information regarding homologs in other Listeria species. Here, we have used a computational evolutionary approach to identify InlP homologs in additional Listeria species. We found that Listeria ivanovii londoniensis (Liv) and Listeria seeligeri (Ls) encode InlP homologs. We also found InlP-like homologs in Listeria innocua and the recently identified species Listeria costaricensis . All newly identified homologs lack the full-length LRR6 and LRR7 domains found in Lm’s InlP. These findings are informative regarding the evolution of one key Lm virulence factor, InlP, and serve as a springboard for future evolutionary studies of Lm pathogenesis as well as mechanistic studies of Listeria internalins.

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Section: Resultsmentioning

confidence: 99%

Section: Resultsmentioning

confidence: 99%

Section: Discussionmentioning

confidence: 99%

Section: Methodsmentioning

confidence: 99%

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Novel internalin P homologs in Listeria

et al. 2022

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“…We added relevant metadata to each of these homologs, including corresponding NCBI protein accession numbers, protein length, taxID, species, and lineages. We used MolEvolvR (39) and the underlying InterProScan (85) to explore the domain architectures, cellular localizations, and disorder predictions for all ∼27K DciA proteins. The resulting domain architectures (from MolEvolvR) were also appended to each homolog’s metadata.…”

Section: Methodsmentioning

confidence: 99%

DciA helicase operators exhibit diversity across bacterial phyla

Blaine¹,

Burke

Ravi

et al. 2022

Preprint

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A fundamental requirement for life is replication of an organism's DNA. Studies in Escherichia coli and Bacillus subtilis have set the paradigm for how DNA replication occurs in bacteria. During replication initiation in E. coli and B. subtilis, the replicative helicase is loaded onto the DNA at the origin of replication by an ATPase helicase loader. However, most bacteria do not encode homologs to the helicase loaders in E. coli and B. subtilis, raising the question of how helicase activity is facilitated in other bacteria during DNA replication initiation. Recent work has identified the DciA protein as a predicted helicase operator that may perform a function analogous to the helicase loaders in E. coli and B. subtilis. DciA proteins are defined by the presence of a DUF721 domain and are conserved in most bacteria. However, we find that the sequence conservation between DciA proteins across different phyla is very low. Therefore, to comprehensively define the DciA protein family, we took a computational evolutionary approach. These analyses identified diversity in sequence features and domain architectures amongst DciA homologs that were associated with specific phylogenetic lineages. The diversity of DciA proteins elucidated here represents the evolution of helicase operation in bacterial DNA replication, highlights the need for phyla-specific analyses of this fundamental biological process, and is an important example of how research in bacterial DNA replication is necessary in organisms beyond E. coli and B. subtilis.

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