scholarly journals Structure Unveils Relationships between RNA Virus Polymerases

Viruses ◽  
2021 ◽  
Vol 13 (2) ◽  
pp. 313
Author(s):  
Heli A. M. Mönttinen ◽  
Janne J. Ravantti ◽  
Minna M. Poranen
Keyword(s):  
Phylogenetic Tree ◽  
Rna Viruses ◽  
Rna Virus ◽  
Sequence Similarity ◽  
Protein Structures ◽  
Structural Similarity ◽  
Functional Differentiation ◽  
Comparison Method ◽  
Homologous Structure ◽  
Biological Entities

RNA viruses are the fastest evolving known biological entities. Consequently, the sequence similarity between homologous viral proteins disappears quickly, limiting the usability of traditional sequence-based phylogenetic methods in the reconstruction of relationships and evolutionary history among RNA viruses. Protein structures, however, typically evolve more slowly than sequences, and structural similarity can still be evident, when no sequence similarity can be detected. Here, we used an automated structural comparison method, homologous structure finder, for comprehensive comparisons of viral RNA-dependent RNA polymerases (RdRps). We identified a common structural core of 231 residues for all the structurally characterized viral RdRps, covering segmented and non-segmented negative-sense, positive-sense, and double-stranded RNA viruses infecting both prokaryotic and eukaryotic hosts. The grouping and branching of the viral RdRps in the structure-based phylogenetic tree follow their functional differentiation. The RdRps using protein primer, RNA primer, or self-priming mechanisms have evolved independently of each other, and the RdRps cluster into two large branches based on the used transcription mechanism. The structure-based distance tree presented here follows the recently established RdRp-based RNA virus classification at genus, subfamily, family, order, class and subphylum ranks. However, the topology of our phylogenetic tree suggests an alternative phylum level organization.

scholarly journals RepeatsDB in 2021: improved data and extended classification for protein tandem repeat structures

2020 ◽  
Vol 49 (D1) ◽  
pp. D452-D457
Author(s):  
Lisanna Paladin ◽  
Martina Bevilacqua ◽  
Sara Errigo ◽  
Damiano Piovesan ◽  
Ivan Mičetić ◽  
...  
Keyword(s):  
Protein Data Bank ◽  
Tandem Repeat ◽  
Tandem Repeats ◽  
Classification Scheme ◽  
Sequence Similarity ◽  
Protein Structures ◽  
Hierarchical Classification ◽  
Structural Similarity ◽  
Data Bank ◽  
Similarity Class

Abstract The RepeatsDB database (URL: https://repeatsdb.org/) provides annotations and classification for protein tandem repeat structures from the Protein Data Bank (PDB). Protein tandem repeats are ubiquitous in all branches of the tree of life. The accumulation of solved repeat structures provides new possibilities for classification and detection, but also increasing the need for annotation. Here we present RepeatsDB 3.0, which addresses these challenges and presents an extended classification scheme. The major conceptual change compared to the previous version is the hierarchical classification combining top levels based solely on structural similarity (Class > Topology > Fold) with two new levels (Clan > Family) requiring sequence similarity and describing repeat motifs in collaboration with Pfam. Data growth has been addressed with improved mechanisms for browsing the classification hierarchy. A new UniProt-centric view unifies the increasingly frequent annotation of structures from identical or similar sequences. This update of RepeatsDB aligns with our commitment to develop a resource that extracts, organizes and distributes specialized information on tandem repeat protein structures.

scholarly journals NeoRdRp: A comprehensive dataset for identifying RNA-dependent RNA polymerase of various RNA viruses from metatranscriptomic data

2022 ◽  
Author(s):  
Shoichi Sakaguchi ◽  
Syun-ichi Urayama ◽  
Yoshihiro Takaki ◽  
Hong Wu ◽  
Youichi Suzuki ◽  
...  
Keyword(s):  
Rna Polymerase ◽  
Rna Viruses ◽  
Rna Virus ◽  
Sequence Similarity ◽  
Virus Detection ◽  
Detection Methods ◽  
Amino Acid Sequence Similarity ◽  
Sequencing Data ◽  
Rna Dependent Rna Polymerase ◽  
Multiple Sequence

RNA viruses are distributed in various environments, and most RNA viruses have been recently identified by metatranscriptome sequencing. However, due to the high nucleotide diversity of RNA viruses, it is still challenging to identify their sequences. Therefore, this study generated a dataset of RNA-dependent RNA polymerase (RdRp) domains essential for all RNA viruses belonging to Orthornavirae. Also, the collected genes with RdRp domains from various RNA viruses were clustered by amino acid sequence similarity. For each cluster, a multiple sequence alignment was generated, and a hidden Markov model (HMM) profile was created if the number of sequences was greater than five. Using the 1,467 HMM profiles, we detected RdRp domains in the RefSeq RNA virus sequences, combined the hit sequences with the RdRp domains, and reconstructed the HMM profiles. As a result, 2,234 HMM profiles were generated from 12,316 RdRp domain sequences, and the dataset was named NeoRdRp. Additionally, using the UniProt dataset, we confirmed that almost all NeoRdRp HMM profiles could specifically detect RdRps in Orthornavirae. Furthermore, we compared the NeoRdRp dataset with two previously reported RNA virus detection methods to detect RNA virus sequences from metatranscriptome sequencing data. Our methods can identify most of the RNA viruses in the datasets; however, some RNA viruses were not detected, similar to the other two methods. The NeoRdRp can be improved by repeatedly adding new RdRp sequences and can be expected to be widely applied as a system for detecting various RNA viruses from metatranscriptome data.

scholarly journals Ancient gene duplications in RNA viruses revealed by protein tertiary structure comparisons

2021 ◽  
Vol 7 (1) ◽  
Author(s):  
Alejandro Miguel Cisneros-Martínez ◽  
Arturo Becerra ◽  
Antonio Lazcano
Keyword(s):  
Tertiary Structure ◽  
Rna Viruses ◽  
Rna Virus ◽  
Protein Structures ◽  
Data Bank ◽  
Cysteine Proteases ◽  
Gene Duplications ◽  
Virus Family ◽  
Protein Tertiary Structure ◽  
Duplication Events

Abstract To date only a handful of duplicated genes have been described in RNA viruses. This shortage can be attributed to different factors, including the RNA viruses with high mutation rate that would make a large genome more prone to acquire deleterious mutations. This may explain why sequence-based approaches have only found duplications in their most recent evolutionary history. To detect earlier duplications, we performed protein tertiary structure comparisons for every RNA virus family represented in the Protein Data Bank. We present a list of thirty pairs of possible paralogs with <30 per cent sequence identity. It is argued that these pairs are the outcome of six duplication events. These include the α and β subunits of the fungal toxin KP6 present in the dsRNA Ustilago maydis virus (family Totiviridae), the SARS-CoV (Coronaviridae) nsp3 domains SUD-N, SUD-M and X-domain, the Picornavirales (families Picornaviridae, Dicistroviridae, Iflaviridae and Secoviridae) capsid proteins VP1, VP2 and VP3, and the Enterovirus (family Picornaviridae) 3C and 2A cysteine-proteases. Protein tertiary structure comparisons may reveal more duplication events as more three-dimensional protein structures are determined and suggests that, although still rare, gene duplications may be more frequent in RNA viruses than previously thought. Keywords: gene duplications; RNA viruses.

scholarly journals Revealing RNA virus diversity and evolution in unicellular algae transcriptomes

2021 ◽  
Author(s):  
Justine Charon ◽  
Shauna Murray ◽  
Edward C Holmes
Keyword(s):  
Rna Viruses ◽  
Rna Virus ◽  
Sequence Similarity ◽  
Sequence Divergence ◽  
Virus Species ◽  
Sequencing Project ◽  
Virus Diversity ◽  
Microbial Eukaryotes ◽  
Unicellular Algae ◽  
Positive Sense

Remarkably little is known about the diversity and evolution of RNA viruses in unicellular eukaryotes. We screened a total of 570 transcriptomes from the Marine Microbial Eukaryote Transcriptome Sequencing Project (MMETSP) project that encompasses a wide diversity of microbial eukaryotes, including most major photosynthetic lineages (i.e. the microalgae). From this, we identified 30 new and divergent RNA virus species, occupying a range of phylogenetic positions within the overall diversity of RNA viruses. Approximately one-third of the newly described viruses comprised single-stranded positive-sense RNA viruses from the order Lenarviricota associated with fungi, plants and protists, while another third were related to the order Ghabrivirales, including members of the protist and fungi-associated Totiviridae. Other viral species showed sequence similarity to positive-sense RNA viruses from the algae-associated Marnaviridae, the double-stranded RNA Partitiviridae, as well as a single negative-sense RNA virus related to the Qinviridae. Importantly, we were able to identify divergent RNA viruses from distant host taxa, revealing the ancestry of these viral families and greatly extending our knowledge of the RNA viromes of microalgal cultures. Both the limited number of viruses detected per sample and the low sequence identity to known RNA viruses imply that additional microalgal viruses exist that could not be detected at the current sequencing depth or were too divergent to be identified using sequence similarity. Together, these results highlight the need for further investigation of algal-associated RNA viruses as well as the development of new tools to identify RNA viruses that exhibit very high levels of sequence divergence.

scholarly journals Metatranscriptomic Identification of Diverse and Divergent RNA Viruses in Green and Chlorarachniophyte Algae Cultures

Viruses ◽  
2020 ◽  
Vol 12 (10) ◽  
pp. 1180
Author(s):  
Justine Charon ◽  
Vanessa Rossetto Marcelino ◽  
Richard Wetherbee ◽  
Heroen Verbruggen ◽  
Edward C. Holmes
Keyword(s):  
Rna Viruses ◽  
Rna Virus ◽  
Sequence Similarity ◽  
Land Plants ◽  
Homology Detection ◽  
Microbial Eukaryotes ◽  
Virus Transfer ◽  
History Of ◽  
First Time ◽  
Distant Homolog

Our knowledge of the diversity and evolution of the virosphere will likely increase dramatically with the study of microbial eukaryotes, including the microalgae within which few RNA viruses have been documented. By combining total RNA sequencing with sequence and structural-based homology detection, we identified 18 novel RNA viruses in cultured samples from two major groups of microbial algae: the chlorophytes and the chlorarachniophytes. Most of the RNA viruses identified in the green algae class Ulvophyceae were related to the Tombusviridae and Amalgaviridae viral families commonly associated with land plants. This suggests that the evolutionary history of these viruses extends to divergence events between algae and land plants. Seven Ostreobium sp-associated viruses exhibited sequence similarity to the mitoviruses most commonly found in fungi, compatible with horizontal virus transfer between algae and fungi. We also document, for the first time, RNA viruses associated with chlorarachniophytes, including the first negative-sense (bunya-like) RNA virus in microalgae, as well as a distant homolog of the plant virus Virgaviridae, potentially signifying viral inheritance from the secondary chloroplast endosymbiosis that marked the origin of the chlorarachniophytes. More broadly, these data suggest that the scarcity of RNA viruses in algae results from limited investigation rather than their absence.

scholarly journals Meta-transcriptomic detection of diverse and divergent RNA viruses in green and chlorarachniophyte algae

2020 ◽  
Author(s):  
Justine Charon ◽  
Vanessa Rossetto Marcelino ◽  
Richard Wetherbee ◽  
Heroen Verbruggen ◽  
Edward C. Holmes
Keyword(s):  
Rna Viruses ◽  
Rna Virus ◽  
Past History ◽  
Protein Structures ◽  
Cultivated Plants ◽  
Secondary Endosymbiosis ◽  
Homology Detection ◽  
Virus Family ◽  
Virus Diversity ◽  
Eukaryotic Microorganisms

AbstractOur knowledge of the diversity and evolution of the virosphere will likely increase dramatically with the study of microbial eukaryotes, including the microalgae in few RNA viruses have been documented to date. By combining meta-transcriptomic approaches with sequence and structural-based homology detection, followed by PCR confirmation, we identified 18 novel RNA viruses in two major groups of microbial algae – the chlorophytes and the chlorarachniophytes. Most of the RNA viruses identified in the green algae class Ulvophyceae were related to those from the families Tombusviridae and Amalgaviridae that have previously been associated with plants, suggesting that these viruses have an evolutionary history that extends to when their host groups shared a common ancestor. In contrast, seven ulvophyte associated viruses exhibited clear similarity with the mitoviruses that are most commonly found in fungi. This is compatible with horizontal virus transfer between algae and fungi, although mitoviruses have recently been documented in plants. We also document, for the first time, RNA viruses in the chlorarachniophytes, including the first observation of a negative-sense (bunya-like) RNA virus in microalgae. The other virus-like sequence detected in chlorarachniophytes is distantly related to those from the plant virus family Virgaviridae, suggesting that they may have been inherited from the secondary chloroplast endosymbiosis event that marked the origin of the chlorarachniophytes. More broadly, this work suggests that the scarcity of RNA viruses in algae most likely results from limited investigation rather than their absence. Greater effort is needed to characterize the RNA viromes of unicellular eukaryotes, including through structure-based methods that are able to detect distant homologies, and with the inclusion of a wider range of eukaryotic microorganisms.Author summaryRNA viruses are expected to infect all living organisms on Earth. Despite recent developments in and the deployment of large-scale sequencing technologies, our understanding of the RNA virosphere remains anthropocentric and largely restricted to human, livestock, cultivated plants and vectors for viral disease. However, a broader investigation of the diversity of RNA viruses, especially in protists, is expected to answer fundamental questions about their origin and long-term evolution. This study first investigates the RNA virus diversity in unicellular algae taxa from the phylogenetically distinct ulvophytes and chlorarachniophytes taxa. Despite very high levels of sequence divergence, we were able to identify 18 new RNA viruses, largely related to plant and fungi viruses, and likely illustrating a past history of horizontal transfer events that have occurred during RNA virus evolution. We also hypothesise that the sequence similarity between a chlorarachniophyte-associated virga-like virus and members of Virgaviridae associated with plants may represent inheritance from a secondary endosymbiosis event. A promising approach to detect the signals of distant virus homologies through the analysis of protein structures was also utilised, enabling us to identify potential highly divergent algal RNA viruses.

Insights into the biochemical and functional characterization of sortase E transpeptidase of Corynebacterium glutamicum

2019 ◽  
Vol 476 (24) ◽  
pp. 3835-3847 ◽  
Author(s):  
Aliyath Susmitha ◽  
Kesavan Madhavan Nampoothiri ◽  
Harsha Bajaj
Keyword(s):  
Protein Engineering ◽  
Cell Attachment ◽  
Functional Characterization ◽  
Protein Structures ◽  
Structural Similarity ◽  
Surface Proteins ◽  
Sortase A ◽  
Peptide Cleavage ◽  
New Findings

Most Gram-positive bacteria contain a membrane-bound transpeptidase known as sortase which covalently incorporates the surface proteins on to the cell wall. The sortase-displayed protein structures are involved in cell attachment, nutrient uptake and aerial hyphae formation. Among the six classes of sortase (A–F), sortase A of S. aureus is the well-characterized housekeeping enzyme considered as an ideal drug target and a valuable biochemical reagent for protein engineering. Similar to SrtA, class E sortase in GC rich bacteria plays a housekeeping role which is not studied extensively. However, C. glutamicum ATCC 13032, an industrially important organism known for amino acid production, carries a single putative sortase (NCgl2838) gene but neither in vitro peptide cleavage activity nor biochemical characterizations have been investigated. Here, we identified that the gene is having a sortase activity and analyzed its structural similarity with Cd-SrtF. The purified enzyme showed a greater affinity toward LAXTG substrate with a calculated KM of 12 ± 1 µM, one of the highest affinities reported for this class of enzyme. Moreover, site-directed mutation studies were carried to ascertain the structure functional relationship of Cg-SrtE and all these are new findings which will enable us to perceive exciting protein engineering applications with this class of enzyme from a non-pathogenic microbe.

scholarly journals Essential role of IPS-1 in innate immune responses against RNA viruses

2006 ◽  
Vol 203 (7) ◽  
pp. 1795-1803 ◽  
Author(s):  
Himanshu Kumar ◽  
Taro Kawai ◽  
Hiroki Kato ◽  
Shintaro Sato ◽  
Ken Takahashi ◽  
...  
Keyword(s):  
Rna Viruses ◽  
Rna Virus ◽  
Critical Role ◽  
Nuclear Factor Κb ◽  
Type I ◽  
Innate Immune Responses ◽  
Antiviral Responses ◽  
Deficient Mice

IFN-β promoter stimulator (IPS)-1 was recently identified as an adapter for retinoic acid–inducible gene I (RIG-I) and melanoma differentiation-associated gene 5 (Mda5), which recognize distinct RNA viruses. Here we show the critical role of IPS-1 in antiviral responses in vivo. IPS-1–deficient mice showed severe defects in both RIG-I– and Mda5-mediated induction of type I interferon and inflammatory cytokines and were susceptible to RNA virus infection. RNA virus–induced interferon regulatory factor-3 and nuclear factor κB activation was also impaired in IPS-1–deficient cells. IPS-1, however, was not essential for the responses to either DNA virus or double-stranded B-DNA. Thus, IPS-1 is the sole adapter in both RIG-I and Mda5 signaling that mediates effective responses against a variety of RNA viruses.

RNA viruses and the mitogenic Raf/MEK/ERK signal transduction cascade

2008 ◽  
Vol 389 (10) ◽  
Author(s):  
Stephan Pleschka
Keyword(s):  
Signal Transduction ◽  
Rna Viruses ◽  
Rna Virus ◽  
Cell Metabolism ◽  
Mitogen Activated Protein Kinase ◽  
Erk Signaling ◽  
Control Center ◽  
Signal Transduction Cascade ◽  
Host Interaction ◽  
Differentiation And Proliferation

AbstractThe Raf/MEK/ERK signal transduction cascade belongs to the mitogen-activated protein kinase (MAPK) cascades. Raf/MEK/ERK signaling leads to stimulus-specific changes in gene expression, alterations in cell metabolism or induction of programmed cell death (apoptosis), and thus controls cell differentiation and proliferation. It is induced by extracellular agents, including pathogens such as RNA viruses. Many DNA viruses are known to induce cellular signaling via this pathway. As these pathogens partly use the DNA synthesis machinery for their replication, they aim to drive cells into a proliferative state. In contrast, the consequences of RNA virus-induced Raf/MEK/ERK signaling were less clear for a long time, but since the turn of the century the number of publications on this topic has rapidly increased. Research on this virus/host-interaction will broaden our understanding of its relevance in viral replication. This important control center of cellular responses is differently employed to support the replication of several important human pathogenic RNA viruses including influenza, Ebola, hepatitis C and SARS corona viruses.

scholarly journals Structural and functional analysis of the Na+/H+ exchanger

2007 ◽  
Vol 401 (3) ◽  
pp. 623-633 ◽  
Author(s):  
Emily R. Slepkov ◽  
Jan K. Rainey ◽  
Brian D. Sykes ◽  
Larry Fliegel
Keyword(s):  
Intracellular Ph ◽  
Sequence Similarity ◽  
Structural Data ◽  
Structural Similarity ◽  
Integral Membrane Protein ◽  
Volume Control ◽  
Amino Acid Residues ◽  
Physiological Processes ◽  
High Resolution Structure ◽  
Extracellular Sodium

The mammalian NHE (Na+/H+ exchanger) is a ubiquitously expressed integral membrane protein that regulates intracellular pH by removing a proton in exchange for an extracellular sodium ion. Of the nine known isoforms of the mammalian NHEs, the first isoform discovered (NHE1) is the most thoroughly characterized. NHE1 is involved in numerous physiological processes in mammals, including regulation of intracellular pH, cell-volume control, cytoskeletal organization, heart disease and cancer. NHE comprises two domains: an N-terminal membrane domain that functions to transport ions, and a C-terminal cytoplasmic regulatory domain that regulates the activity and mediates cytoskeletal interactions. Although the exact mechanism of transport by NHE1 remains elusive, recent studies have identified amino acid residues that are important for NHE function. In addition, progress has been made regarding the elucidation of the structure of NHEs. Specifically, the structure of a single TM (transmembrane) segment from NHE1 has been solved, and the high-resolution structure of the bacterial Na+/H+ antiporter NhaA has recently been elucidated. In this review we discuss what is known about both functional and structural aspects of NHE1. We relate the known structural data for NHE1 to the NhaA structure, where TM IV of NHE1 shows surprising structural similarity with TM IV of NhaA, despite little primary sequence similarity. Further experiments that will be required to fully understand the mechanism of transport and regulation of the NHE1 protein are discussed.

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