Dendroscope: An interactive viewer for large phylogenetic trees

Huson, Daniel H.; Richter, Daniel C.; Rausch, Christian; Dezulian, Tobias; Franz, Markus; Rupp, Regula

doi:10.1186/1471-2105-8-460

Cited by 1,109 publications

(806 citation statements)

References 11 publications

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“…Monte Carlo Markov chains were run for 1 million generations, and the initial 25% of trees were discarded as burn in. Phylograms were visualized using Dendroscope (56). Phylogenetic trees were generated for both the whole-protein sequences and the MACPF/CDC-like domains.…”

Section: Methodsmentioning

confidence: 99%

Stonefish toxin defines an ancient branch of the perforin-like superfamily

Ellisdon

Reboul

Panjikar

et al. 2015

Proc. Natl. Acad. Sci. U.S.A.

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The lethal factor in stonefish venom is stonustoxin (SNTX), a heterodimeric cytolytic protein that induces cardiovascular collapse in humans and native predators. Here, using X-ray crystallography, we make the unexpected finding that SNTX is a pore-forming member of an ancient branch of the Membrane Attack ComplexPerforin/Cholesterol-Dependent Cytolysin (MACPF/CDC) superfamily. SNTX comprises two homologous subunits (α and β), each of which comprises an N-terminal pore-forming MACPF/CDC domain, a central focal adhesion-targeting domain, a thioredoxin domain, and a C-terminal tripartite motif family-like PRY SPla and the RYanodine Receptor immune recognition domain. Crucially, the structure reveals that the two MACPF domains are in complex with one another and arranged into a stable early prepore-like assembly. These data provide long sought after near-atomic resolution insights into how MACPF/CDC proteins assemble into prepores on the surface of membranes. Furthermore, our analyses reveal that SNTX-like MACPF/CDCs are distributed throughout eukaryotic life and play a broader, possibly immune-related function outside venom.H uman envenoming by the tropical stonefish (Synanceia horrida and related species) results in extreme pain, edema, hypotension, respiratory distress, and on rare occasions, death (1). The lethal factor in stonefish venom is an ∼150-kDa protein termed stonustoxin (SNTX), an unusual example of a vertebrate cytolytic protein complex (2). SNTX is a soluble heterodimeric assembly of two closely related proteins termed SNTX-α and -β that share sequence identity of ∼50% (3). With the exception of a C-terminal PRY SPla and the RYanodine Receptor (PRYSPRY) domain in each protein (4), SNTX shares no obvious sequence similarity to any structurally or functionally characterized molecule. SNTX induces species-specific hemolytic activity (2) by an apparent pore-forming mechanism (5). It induces platelet aggregation (6), and like the closely related Trachynilysin (from Synanceia trachynis), SNTX exhibits activity suggesting that it may function as a neurotoxin (7,8).Because eukaryote pore-forming toxins are relatively rare, we reasoned that SNTX might represent a new exemplar of a vertebrate pore-forming protein. Previous studies had shown that it was possible to purify and crystallize SNTX (9); however, no structure has been reported to date. Accordingly, to address the structural basis for SNTX activity, we determined its X-ray crystal structure.

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Section: Methodsmentioning

confidence: 99%

Stonefish toxin defines an ancient branch of the perforin-like superfamily

Ellisdon

Reboul

Panjikar

et al. 2015

Proc. Natl. Acad. Sci. U.S.A.

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“…rtxA1, and concatenated MLST sequences were aligned using CLUSTALW and the phylogeny determined with PHYLIP using the Workbench 3.2 interface at the San Diego Supercomputer Center. Neighbor-joining trees for publication were prepared from the Newick output using Dendroscope 2.7.4 (29)(30)(31)(32)(33). The bootstrap confidence values (1,000 replicates) were determined using MacVector 10.5.1 sequence alignment software package.…”

Section: Methodsmentioning

confidence: 99%

Vibrio vulnificus rtxA1 gene recombination generates toxin variants with altered potency during intestinal infection

Kwak

Jeong

Satchell

2011

Proc. Natl. Acad. Sci. U.S.A.

143

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Vibrio vulnificus is a food-borne bacterial pathogen associated with 1% of all food-related deaths, predominantly because of consumption of contaminated seafood. The ability of V. vulnificus to cause disease is linked to the production of a large cytotoxin called the "multifunctional-autoprocessing RTX" (MARTX Vv ) toxin, a factor shown here to be an important virulence factor by the intragastric route of infection in mice. In this study, we examined genetic variation of the rtxA1 gene that encodes MARTX Vv in 40 V. vulnificus Biotype 1 strains and found four distinct variants of rtxA1 that encode toxins with different arrangements of effector domains. We provide evidence that these variants arose by recombination either with rtxA genes carried on plasmids or with the rtxA gene of Vibrio anguillarum. Contrary to expected results, the most common rtxA1 gene variant in clinical-type V. vulnificus encodes a toxin with reduced potency and is distinct from the toxin produced by strains isolated from market oysters. These results indicate that an important virulence factor of V. vulnificus is undergoing significant genetic rearrangement and may be subject to selection for reduced virulence in the environment. This finding would imply further that in the future on-going genetic variation of the MARTX Vv toxins could result in the emergence of novel strains with altered virulence in humans.phylogeny | RTX | oyster T he gram-negative bacterial pathogen Vibrio vulnificus inhabits coastal waters including the US Gulf Coast. The pathogen causes gastroenteritis, primary septicemia, and necrotizing fasciitis and can be difficult to treat. The bacteria are particularly rapid growers in vivo and are highly invasive; thus death can occur as quickly as 24-48 h after ingestion (1, 2). In the United States from 1998-2008, 985 cases of V. vulnificus infection resulting in 91 deaths were reported to the Centers for Disease Control. Of these cases, 60% were caused by food-borne illness, particularly associated with the consumption of raw seafood (3). In fact, V. vulnificus accounts for 1% of all food-related deaths in the United States (4). Numerous studies recently have described a V. vulnificus multifunctional-autoprocessing RTX toxin (MARTX Vv ) as having a major impact on virulence in mice (5-8). Toxins of the MARTX family are very large composite toxins. The 5,206-amino acid MARTX Vv toxin as found in the two sequenced strains of V. vulnificus, Korean isolate CMCP6 and Taiwanese isolate YJ016 (9, 10), are 99% identical. Similar to all MARTX toxins, the majority of MARTX Vv is comprised of conserved repeat regions at the N and C termini that are proposed to form a pore in the eukaryotic cell plasma membrane for translocation of the central portion of the secreted toxin to the cytosol (11). The central region includes a conserved cysteine protease domain (CPD) that is required for inositol hexakisphosphate-induced autoprocessing. After translocation, autoprocessing at leucine residues in unstructured regions between the effector do...

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“…Sequences with Ͼ95% identity were removed using Skipredundant from the EMBOSS software suite (40). The resulting set of sequences was aligned using the program MUSCLE (12), and a neighbor-joining tree was constructed with 1,000 bootstrap steps using Clustal W, version 2.0 (27), and visualized by aid of Dendroscope (20) and Inkscape (http://inkscape.org). The organization of O16G-and G16G-encoding genes from various organisms was investigated using the genome database provided by the National Center for Biotechnology Information (NCBI), U.S. National Library of Medicine (http://www.ncbi.nlm .nih.gov/genomes/lproks.cgi).…”

Section: Methodsmentioning

confidence: 99%

Enzymology and Structure of the GH13_31 Glucan 1,6-α-Glucosidase That Confers Isomaltooligosaccharide Utilization in the Probiotic Lactobacillus acidophilus NCFM

et al. 2012

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b Isomaltooligosaccharides (IMO) have been suggested as promising prebiotics that stimulate the growth of probiotic bacteria. Genomes of probiotic lactobacilli from the acidophilus group, as represented by Lactobacillus acidophilus NCFM, encode ␣-1,6 glucosidases of the family GH13_31 (glycoside hydrolase family 13 subfamily 31) that confer degradation of IMO. These genes reside frequently within maltooligosaccharide utilization operons, which include an ATP-binding cassette transporter and ␣-glucan active enzymes, e.g., maltogenic amylases and maltose phosphorylases, and they also occur separated from any carbohydrate transport or catabolism genes on the genomes of some acidophilus complex members, as in L. acidophilus NCFM. Besides the isolated locus encoding a GH13_31 enzyme, the ABC transporter and another GH13 in the maltooligosaccharide operon were induced in response to IMO or maltotetraose, as determined by reverse transcription-PCR (RT-PCR) transcriptional analysis, suggesting coregulation of ␣-1,6-and ␣-1,4-glucooligosaccharide utilization loci in L. acidophilus NCFM. The L. acidophilus NCFM GH13_31 (LaGH13_31) was produced recombinantly and shown to be a glucan 1,6-␣-glucosidase active on IMO and dextran and product-inhibited by glucose. The catalytic efficiency of LaGH13_31 on dextran and the dextran/panose (trisaccharide) efficiency ratio were the highest reported for this class of enzymes, suggesting higher affinity at distal substrate binding sites. The crystal structure of LaGH13_31 was determined to a resolution of 2.05 Å and revealed additional substrate contacts at the ؉2 subsite in LaGH13_31 compared to the GH13_31 from Streptococcus mutans (SmGH13_31), providing a possible structural rationale to the relatively high affinity for dextran. A comprehensive phylogenetic and activity motif analysis mapped IMO utilization enzymes from gut microbiota to rationalize preferential utilization of IMO by gut residents.

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Dendroscope: An interactive viewer for large phylogenetic trees

Cited by 1,109 publications

References 11 publications

Stonefish toxin defines an ancient branch of the perforin-like superfamily

Stonefish toxin defines an ancient branch of the perforin-like superfamily

Vibrio vulnificus rtxA1 gene recombination generates toxin variants with altered potency during intestinal infection

Enzymology and Structure of the GH13_31 Glucan 1,6-α-Glucosidase That Confers Isomaltooligosaccharide Utilization in the Probiotic Lactobacillus acidophilus NCFM

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