T-Coffee: a web server for the multiple sequence alignment of protein and RNA sequences using structural information and homology extension

Tommaso, Paolo Di; Moretti, Sébastien; Xenarios, Ioannis; Orobitg, Miquel; Montanyola, Alberto; Chang, Jia‐Ming; Taly, Jean-François; Notredame, Cédric

doi:10.1093/nar/gkr245

Cited by 996 publications

(739 citation statements)

References 25 publications

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“…Those predicted tRNAs with CAG anticodons (complement of CUG) were chosen and designated as tRNA CAG . Secondary structure-based multiple alignment of predicted tRNA CAG sequences was then performed with R-Coffee (44). Resulting alignments were manually inspected to identify the sequence features previously described (9) as important for translation of CUG to Ser (SI Appendix, Fig.…”

Section: Methodsmentioning

confidence: 99%

Comparative genomics of biotechnologically important yeasts

Riley

Haridas

Wolfe

et al. 2016

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

303

394

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Ascomycete yeasts are metabolically diverse, with great potential for biotechnology. Here, we report the comparative genome analysis of 29 taxonomically and biotechnologically important yeasts, including 16 newly sequenced. We identify a genetic code change, CUG-Ala, in Pachysolen tannophilus in the clade sister to the known CUG-Ser clade. Our well-resolved yeast phylogeny shows that some traits, such as methylotrophy, are restricted to single clades, whereas others, such as L-rhamnose utilization, have patchy phylogenetic distributions. Gene clusters, with variable organization and distribution, encode many pathways of interest. Genomics can predict some biochemical traits precisely, but the genomic basis of others, such as xylose utilization, remains unresolved. Our data also provide insight into early evolution of ascomycetes. We document the loss of H3K9me2/3 heterochromatin, the origin of ascomycete mating-type switching, and panascomycete synteny at the MAT locus. These data and analyses will facilitate the engineering of efficient biosynthetic and degradative pathways and gateways for genomic manipulation.genomics | bioenergy | biotechnological yeasts | genetic code | microbiology Y easts are fungi that reproduce asexually by budding or fission and sexually without multicellular fruiting bodies (1, 2). Their unicellular, largely free-living lifestyle has evolved several times (3). Despite morphological similarities, yeasts constitute over 1,500 known species that inhabit many specialized environmental niches and associations, including virtually all varieties of fruits and flowers, plant surfaces and exudates, insects and other invertebrates, birds, mammals, and highly diverse soils (4). Biochemical and genomic studies of the model yeast Saccharomyces cerevisiaeessential for making bread, beer, and wine-have established much of our understanding of eukaryotic biology. However, in many ways, S. cerevisiae is an oddity among the yeasts, and many important biotechnological applications and highly divergent physiological capabilities of lesser-known yeast species have not been fully exploited (5). Various species can grow on methanol or n-alkanes as sole carbon and energy sources, overproduce vitamins and lipids, thrive under acidic conditions, and ferment unconventional carbon sources. Many features of yeasts make them ideal platforms for biotechnological processes. Their thick cell walls help them survive osmotic shock, and in contrast to bacteria, they are resistant to viruses. Their unicellular form is easy to cultivate, scale up, and harvest. The objective of this study was, therefore, to put yeasts with diverse biotechnological applications in a phylogenomic context and relate their physiologies to genomic SignificanceThe highly diverse Ascomycete yeasts have enormous biotechnological potential. Collectively, these yeasts convert a broad range of substrates into useful compounds, such as ethanol, lipids, and vitamins, and can grow in extremes of temperature, salinity, and pH. We compared 29 yeast genome...

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Section: Methodsmentioning

confidence: 99%

Comparative genomics of biotechnologically important yeasts

Riley

Haridas

Wolfe

et al. 2016

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

303

394

View full text Add to dashboard Cite

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“…Identification of a conserved eIF2α-binding motif in GADD34. Multiple sequence alignment of the C-terminal portion of human GADD34 and 31 related proteins was built by using the T-coffee web server (48,49). Numbers correspond to residue positions in the full-length proteins.…”

Section: Gadd34 Promotesmentioning

confidence: 99%

An eIF2α-binding motif in protein phosphatase 1 subunit GADD34 and its viral orthologs is required to promote dephosphorylation of eIF2α

Rojas

Vasconcelos

Dever

2015

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

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Transient protein synthesis inhibition, mediated by phosphorylation of the α subunit of eukaryotic translation initiation factor 2 (eIF2α), is an important protective mechanism cells use during stress conditions. Following relief of the stress, the growth arrest and DNA damage-inducible protein GADD34 associates with the broadly acting serine/threonine protein phosphatase 1 (PP1) to dephosphorylate eIF2α. Whereas the PP1-binding motif on GADD34 has been defined, it remains to be determined how GADD34 directs PP1 to specifically dephosphorylate eIF2α. In this report, we map a novel eIF2α-binding motif to the C terminus of GADD34 in a region distinct from where PP1 binds to GADD34. This motif is characterized by the consensus sequence Rx [Gnl], where capital letters are preferred and x is any residue. Point mutations altering the eIF2α-binding motif impair the ability of GADD34 to interact with eIF2α, promote eIF2α dephosphorylation, and suppress PKR toxicity in yeast. Interestingly, this eIF2α-docking motif is conserved among viral orthologs of GADD34, and is necessary for the proteins produced by African swine fever virus, Canarypox virus, and Herpes simplex virus to promote eIF2α dephosphorylation. Taken together, these data indicate that GADD34 and its viral orthologs direct specific dephosphorylation of eIF2α by interacting with both PP1 and eIF2α through independent binding motifs.

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“…ML1419c haem-binding sites were identified from the NCBI CDD. Alignment of M. leprae strain TN protein sequences possessing GGDEF and/or EAL motifs was performed with the T-Coffee alignment tool (Di Tommaso et al, 2011). Evaluation of putative transmembrane domains was performed with TMHMM program (http:// www.cbs.dtu.dk/services/TMHMM/) (Krogh et al, 2001).…”

Section: Methodsmentioning

confidence: 99%

“…Multiple alignments of the M. leprae proteins containing GGDEF and EAL domains (Figs 1e and S1a) were performed with T-Coffee (Di Tommaso et al, 2011). This demonstrated conservation of key amino acids in putative active sites.…”

Section: Bioinformatics Analyses and Identification Of Cyclic Di-gmp-mentioning

confidence: 99%

Diguanylate cyclase activity of the Mycobacterium leprae T cell antigen ML1419c

et al. 2016

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The second messenger, bis-(3¢,5¢)-cyclic dimeric guanosine monophosphate (cyclic di-GMP), is involved in the control of multiple bacterial phenotypes, including those that impact host-pathogen interactions. Bioinformatics analyses predicted that Mycobacterium leprae, an obligate intracellular bacterium and the causative agent of leprosy, encodes three active diguanylate cyclases. In contrast, the related pathogen Mycobacterium tuberculosis encodes only a single diguanylate cyclase. One of the M. leprae unique diguanylate cyclases (ML1419c) was previously shown to be produced early during the course of leprosy. Thus, functional analysis of ML1419c was performed. The gene encoding ML1419c was cloned and expressed in Pseudomonas aeruginosa PAO1 to allow for assessment of cyclic di-GMP production and cyclic di-GMP-mediated phenotypes. Phenotypic studies revealed that ml1419c expression altered colony morphology, motility and biofilm formation of P. aeruginosa PAO1 in a manner consistent with increased cyclic di-GMP production. Direct measurement of cyclic di-GMP levels by liquid chromatography-mass spectrometry confirmed that ml1419c expression increased cyclic di-GMP production in P. aeruginosa PAO1 cultures in comparison to the vector control. The observed phenotypes and increased levels of cyclic di-GMP detected in P. aeruginosa expressing ml1419c could be abrogated by mutation of the active site in ML1419c. These studies demonstrated that ML1419c of M. leprae functions as diguanylate cyclase to synthesize cyclic di-GMP. Thus, this protein was renamed DgcA (Diguanylate cyclase A). These results also demonstrated the ability to use P. aeruginosa as a heterologous host for characterizing the function of proteins involved in the cyclic di-GMP pathway of a pathogen refractory to in vitro growth, M. leprae.

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T-Coffee: a web server for the multiple sequence alignment of protein and RNA sequences using structural information and homology extension

Cited by 996 publications

References 25 publications

Comparative genomics of biotechnologically important yeasts

Comparative genomics of biotechnologically important yeasts

An eIF2α-binding motif in protein phosphatase 1 subunit GADD34 and its viral orthologs is required to promote dephosphorylation of eIF2α

Diguanylate cyclase activity of the Mycobacterium leprae T cell antigen ML1419c

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