Advantages of combined transmembrane topology and signal peptide prediction--the Phobius web server

Käll, Lukas; Krogh, Anders; Sonnhammer, Erik L. L.

doi:10.1093/nar/gkm256

Cited by 1,509 publications

(1,241 citation statements)

References 14 publications

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“…A mixture model approach identified 99% percentile probability of being in contact. We used a combination of commonly used prediction methods to determine secondary structure predictions (PSIPRED 30 and PolyPhobius 31 ) together with secondary structure propensity computed directly from local ECs 29 resulting in the identification 10 TM helices and 3 smaller helices in ECL4 and 2 beta-strands in ECL2. A total of 220 folded models for T. thermophilus RodA were generated for increasing numbers of EC restraints with using the folding protocol in EVfold 9 which itself uses a distance geometry and simulated annealing protocol in CNS 32,33 .…”

Section: Methodsmentioning

confidence: 99%

Structure of the peptidoglycan polymerase RodA resolved by evolutionary coupling analysis

Sjodt

Brock

Dobihal

et al. 2018

Nature

120

139

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The Shape, Elongation, Division, and Sporulation (“SEDS”) proteins are a large family of ubiquitous and essential transmembrane enzymes with critical roles in bacterial cell wall biology. The exact function of SEDS proteins was long enigmatic, but recent work1–3 has revealed that the prototypical SEDS family member RodA is a peptidoglycan polymerase – a role previously attributed exclusively to members of the penicillin binding protein family4. This discovery has made RodA and other SEDS proteins promising targets for the development of next-generation antibiotics. However, little is known regarding the molecular basis for SEDS activity, and no structural data are available for RodA or any homolog thereof. Here, we report the crystal structure of Thermus thermophilus RodA at a resolution of 2.9 Å, determined using evolutionary covariance-based fold prediction to enable molecular replacement. The structure reveals a novel ten-pass transmembrane fold with large extracellular loops, one of which is partially disordered. The protein contains a highly conserved cavity in the transmembrane domain, reminiscent of ligand binding sites in transmembrane receptors. Mutagenesis experiments in Bacillus subtilis and Escherichia coli show that perturbation of this cavity abolishes RodA function both in vitro and in vivo, indicating it is catalytically essential. These results provide a framework for understanding bacterial cell wall synthesis and SEDS protein function.

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Section: Methodsmentioning

confidence: 99%

Structure of the peptidoglycan polymerase RodA resolved by evolutionary coupling analysis

Sjodt

Brock

Dobihal

et al. 2018

Nature

120

139

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“…Four algorithms were used to predict integral membrane proteins (IMPs) and transmembrane helices (TMH): TMHMM2.0 (39, 56), SOSUI1.1 (23,45,46), HMMTOP2.0 (61,62), and Phobius (37,38). Signal peptides were predicted using LipoP1.0 (34), SignalP3.0 (5, 47), and Phobius.…”

Section: Methodsmentioning

confidence: 99%

A Comprehensive Proteomics and Transcriptomics Analysis ofBacillus subtilisSalt Stress Adaptation

et al. 2010

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In its natural habitats, Bacillus subtilis is exposed to changing osmolarity, necessitating adaptive stress responses. Transcriptomic and proteomic approaches can provide a picture of the dynamic changes occurring in salt-stressed B. subtilis cultures because these studies provide an unbiased view of cells coping with high salinity. We applied whole-genome microarray technology and metabolic labeling, combined with state-of-theart proteomic techniques, to provide a global and time-resolved picture of the physiological response of B. subtilis cells exposed to a severe and sudden osmotic upshift. This combined experimental approach provided quantitative data for 3,961 mRNA transcription profiles, 590 expression profiles of proteins detected in the cytosol, and 383 expression profiles of proteins detected in the membrane fraction. Our study uncovered a well-coordinated induction of gene expression subsequent to an osmotic upshift that involves large parts of the SigB, SigW, SigM, and SigX regulons. Additionally osmotic upregulation of a large number of genes that do not belong to these regulons was observed. In total, osmotic upregulation of about 500 B. subtilis genes was detected. Our data provide an unprecedented rich basis for further in-depth investigation of the physiological and genetic responses of B. subtilis to hyperosmotic stress.

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“…The redundant sequences were removed with Jalview [9], remaining 199 in the positive dataset. The negative dataset was composed of an equal number of random protein sequences predicted as transmembrane by Phobius [10], totaling 398 sequences in main dataset. For each sequence, four physicochemical properties were calculated: net charge at the physiological pH, ratio between hydrophobic and charged residues, average hydrophobicity (H) and the hydrophobic moment (μH).…”

Section: Methodsmentioning

confidence: 99%

An SVM Model Based on Physicochemical Properties to Predict Antimicrobial Activity from Protein Sequences with Cysteine Knot Motifs

Porto

Fernandes

Franco

2010

Lecture Notes in Computer Science

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Abstract. The cysteine knot motifs are widely spread in several classes of peptides including those with antimicrobial functions. These motifs offer a major stability to the protein structure. Nevertheless, the antimicrobial activity is modulated by physicochemical properties. In this paper, we create a model of support vector machine to predict antimicrobial activity from sequences with similar motifs, based on physicochemical properties: net charge, ratio between hydrophobic and charged residues, average hydrophobicity and hydrophobic moment. The support vector machine model was trained with 146 antimicrobial peptides with six cysteines from the antimicrobial peptides database and an equal number of random sequences predicted as transmembrane proteins. The polynomial kernel shows the best accuracy (77.4%) on 10-fold cross validation. Testing in a blind dataset, we observe an accuracy of 83.02%. Through this model, proteins of varied size with a cysteine knot motif can be predicted with good reliability.

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Advantages of combined transmembrane topology and signal peptide prediction--the Phobius web server

Cited by 1,509 publications

References 14 publications

Structure of the peptidoglycan polymerase RodA resolved by evolutionary coupling analysis

Structure of the peptidoglycan polymerase RodA resolved by evolutionary coupling analysis

A Comprehensive Proteomics and Transcriptomics Analysis ofBacillus subtilisSalt Stress Adaptation

An SVM Model Based on Physicochemical Properties to Predict Antimicrobial Activity from Protein Sequences with Cysteine Knot Motifs

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