Crystal structure of a Thermus aquaticus diversity-generating retroelement variable protein

Handa, Sumit; Shaw, Kharissa L; Ghosh, Partho

doi:10.1371/journal.pone.0205618

Cited by 8 publications

(8 citation statements)

References 42 publications

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“… 2013 ). The exploration of novel DGRs with advantageous properties, such as thermostability (Handa, Shaw and Ghosh 2019 ), could provide promising new tools. In addition, characterization of the mutagenic retrohoming mechanism has revealed that the RT and Avd proteins of the BPP-1 DGR work as a complex and that both are required for cDNA synthesis from both DGR and non-DGR templates with an oligodeoxynucleotide (ODN) primer (Handa et al .…”

Section: Introductionmentioning

confidence: 99%

Prokaryotic reverse transcriptases: from retroelements to specialized defense systems

González-Delgado

Mestre

Martı́nez-Abarca

et al. 2021

FEMS Microbiology Reviews

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Reverse transcriptases (RTs) catalyze the polymerization of DNA from an RNA template. These enzymes were first discovered in RNA tumor viruses in 1970, but it was not until 1989 that they were found in prokaryotes as a key component of retrons. Apart from RTs encoded by the “selfish” mobile retroelements known as group II introns, prokaryotic RTs are extraordinarily diverse, but their function has remained elusive. However, recent studies have revealed that different lineages of prokaryotic RTs, including retrons, those associated with CRISPR-Cas systems, Abi-like RTs, and other yet uncharacterized RTs, are key components of different lines of defense against phages and other mobile genetic elements. Prokaryotic RTs participate in various antiviral strategies, including abortive infection (Abi), in which the infected cell is induced to commit suicide to protect the host population, adaptive immunity, in which a memory of previous infection is used to build an efficient defense, and other as yet unidentified mechanisms. These prokaryotic enzymes are attracting considerable attention, both for use in cutting-edge technologies, such as genome editing, and as an emerging research topic. In this review, we discuss what is known about prokaryotic RTs, and the exciting evidence for their domestication from retroelements to create specialized defense systems.

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Section: Introductionmentioning

confidence: 99%

Prokaryotic reverse transcriptases: from retroelements to specialized defense systems

González-Delgado

Mestre

Martı́nez-Abarca

et al. 2021

FEMS Microbiology Reviews

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“…While DGR target proteins share low sequence identity, the structures of several such proteins have revealed the C-type lectin (CLec) fold as a conserved scaffold for accommodating massive sequence variation (16–18). A recent example is the target protein encoded by a prophage of the thermophile Thermus aquaticus : its variable region is nearly identical in structure to those of several other DGR variable proteins containing the CLec fold despite the low sequence identity among them (17). Wu et al classified the VR-encoding domains of the variable proteins into several classes based on their sequence alignments, including three C-type lectin folds (CLec1, CLec2 and CLec3), two Ig fold classes (named Ig1 and Ig2), and several additional classes of unknown VR domains (3).…”

Section: Introductionmentioning

confidence: 99%

MyDGR: a server for identification and characterization of diversity-generating retroelements

Sharifi

2019

Nucleic Acids Research

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MyDGR is a web server providing integrated prediction and visualization of Diversity-Generating Retroelements (DGR) systems in query nucleotide sequences. It is built upon an enhanced version of DGRscan, a tool we previously developed for identification of DGR systems. DGR systems are remarkable genetic elements that use error-prone reverse transcriptases to generate vast sequence variants in specific target genes, which have been shown to benefit their hosts (bacteria, archaea or phages). As the first web server for annotation of DGR systems, myDGR is freely available on the web at http://omics.informatics.indiana.edu/myDGR with all major browsers supported. MyDGR accepts query nucleotide sequences in FASTA format, and outputs all the important features of a predicted DGR system, including a reverse transcriptase, a template repeat and one (or more) variable repeats and their alignment featuring A-to-N (N can be C, T or G) substitutions, and VR-containing target gene(s). In addition to providing the results as text files for download, myDGR generates a visual summary of the results for users to explore the predicted DGR systems. Users can also directly access pre-calculated, putative DGR systems identified in currently available reference bacterial genomes and a few other collections of sequences (including human microbiomes).

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“…Comparison of the obtained model with protein structures from PDB using the Dali server showed that RBP has a structural similarity with proteins containing the C-type lectin domain ( Figure 10 and Figure S5 ). The highest similarity of the crAssE-Sib RBP was revealed with the TaqVP protein (pdb 5VF4, DALI Z-score 19.7) that is encoded by the gene located in the DGR cassette found in Thermus aquaticus ( Figure 10 and Figure S5 ) [ 51 ]. However, RBP of crAssE-Sib contained an additional N-terminal part that was absent in TaqVP.…”

Section: Resultsmentioning

confidence: 99%

Genome Analysis of Epsilon CrAss-like Phages

Babkin,

Tikunov,

Baykov

et al. 2024

Viruses

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CrAss-like phages play an important role in maintaining ecological balance in the human intestinal microbiome. However, their genetic diversity and lifestyle are still insufficiently studied. In this study, a novel CrAssE-Sib phage genome belonging to the epsilon crAss-like phage genomes was found. Comparative analysis indicated that epsilon crAss-like phages are divided into two putative genera, which were proposed to be named Epsilonunovirus and Epsilonduovirus; CrAssE-Sib belongs to the former. The crAssE-Sib genome contains a diversity-generating retroelement (DGR) cassette with all essential elements, including the reverse transcriptase (RT) and receptor binding protein (RBP) genes. However, this RT contains the GxxxSP motif in its fourth domain instead of the usual GxxxSQ motif found in all known phage and bacterial DGRs. RBP encoded by CrAssE-Sib and other Epsilonunoviruses has an unusual structure, and no similar phage proteins were found. In addition, crAssE-Sib and other Epsilonunoviruses encode conserved prophage repressor and anti-repressors that could be involved in lysogenic-to-lytic cycle switches. Notably, DNA primase sequences of epsilon crAss-like phages are not included in the monophyletic group formed by the DNA primases of all other crAss-like phages. Therefore, epsilon crAss-like phage substantially differ from other crAss-like phages, indicating the need to classify these phages into a separate family.

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Crystal structure of a Thermus aquaticus diversity-generating retroelement variable protein

Cited by 8 publications

References 42 publications

Prokaryotic reverse transcriptases: from retroelements to specialized defense systems

Prokaryotic reverse transcriptases: from retroelements to specialized defense systems

MyDGR: a server for identification and characterization of diversity-generating retroelements

Genome Analysis of Epsilon CrAss-like Phages

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