TOPCONS: consensus prediction of membrane protein topology

Bernsel, Andreas; Viklund, Håkan; Hennerdal, Aron; Elofsson, Arne

doi:10.1093/nar/gkp363

Cited by 500 publications

(419 citation statements)

References 19 publications

(25 reference statements)

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“…As an alternative method to obtain the topology for SaeS and validate our SCAM assignments, we used the SaeS amino acid sequence from LAC for TOPCONS analysis, a consensus topology prediction program (23). A small sensing domain composed of two transmembrane passes connected by a nine amino acid extracellular loop was predicted (depicted in red and blue in Fig.…”

Section: Resultsmentioning

confidence: 99%

Differential regulation of staphylococcal virulence by the sensor kinase SaeS in response to neutrophil-derived stimuli

Flack

Zurek

Meishery

et al. 2014

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

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Two-component systems (TCSs) are highly conserved across bacteria and are used to rapidly sense and respond to changing environmental conditions. The human pathogen Staphylococcus aureus uses the S. aureus exoprotein expression (sae) TCS to sense host signals and activate transcription of virulence factors essential to pathogenesis. Despite its importance, the mechanism by which the histidine kinase SaeS recognizes specific host stimuli is unknown. After mutagenizing the predicted extracellular loop of SaeS, we discovered one methionine residue (M31) was essential for the ability of S. aureus to transcribe sae target genes, including hla, lukAB/lukGH, and hlgA. This single M31A mutation also significantly reduced cytotoxicity in human neutrophils to levels observed in cells following interaction with ΔsaeS. Another important discovery was that mutation of two aromatic anchor residues (W32A and F33A) disrupted the normal basal signaling of SaeS in the absence of inducing signals, yet both mutant kinases had appropriate activation of effector genes following exposure to neutrophils. Although the transcriptional profile of aromatic mutation W32A was consistent with that of WT in response to human α-defensin 1, mutant kinase F33A did not properly transcribe the γ-toxin genes in response to this stimulus. Taken together, our results provide molecular evidence for how SaeS recognizes host signals and triggers activation of select virulence factors to facilitate evasion of innate immunity. These findings have important implications for signal transduction in prokaryotes and eukaryotes due to conservation of aromatic anchor residues across both of these domains and the important role they play in sensor protein structure and function.host-pathogen interactions | membrane proteins

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Section: Resultsmentioning

confidence: 99%

Differential regulation of staphylococcal virulence by the sensor kinase SaeS in response to neutrophil-derived stimuli

Flack

Zurek

Meishery

et al. 2014

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

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“…ZevB does not show these characteristics. Moreover, modeling of ZevB using the consensus prediction of membrane protein topology server (TOPCONS) (8) indicates that it contains only the typical six transmembrane spans present in each of the two transmembrane subunits observed in ABC ATPases (13). This evidence suggests that ZevA and ZevB are partnering components of an ABC ATPase transport system probably involved in substrate influx.…”

Section: Resultsmentioning

confidence: 99%

A Novel Zinc Binding System, ZevAB, Is Critical for Survival of Nontypeable Haemophilus influenzae in a Murine Lung Infection Model

et al. 2011

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Nontypeable Haemophilus influenzae (NTHI) is a Gram-negative bacterial pathogen that causes upper and lower respiratory infections. Factors required for pulmonary infection by NTHI are not well understood. Previously, using high-throughput insertion tracking by deep sequencing (HITS), putative lung colonization factors were identified. Also, previous research indicates that secreted disulfide-dependent factors are important for virulence of H. influenzae. In the present study, HITS data were compared with an informatics-based list of putative substrates of the periplasmic oxidoreductase DsbA to find and characterize secreted virulence factors. This analysis resulted in identification of the "zinc binding essential for virulence" (zev) locus consisting of zevA (HI1249) and zevB (HI1248). NTHI mutants of zevA and zevB grew normally in rich medium but were defective for colonization in a mouse lung model. Mutants also exhibited severe growth defects in medium containing EDTA and were rescued by supplementation with zinc. Additionally, purified recombinant ZevA was found to bind to zinc with high affinity. Together, these data demonstrate that zevAB is a novel virulence factor important for zinc utilization of H. influenzae under conditions where zinc is limiting. Furthermore, evidence presented here suggests that zinc limitation is likely an important mechanism for host defense against pathogens during lung infection.

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“…20 mM L-proline was used for induction of prnB expression, at 25°C for 12-14 h. Samples were observed using a Plan-Apochromat ϫ100 1.40 NA oil immersion objective lens on an Axioplan 2 fluorescence microscope (Carl Zeiss, Inc.) with appropriate filters and the resulting images were acquired with a Zeiss-MRC5 digital camera using AxioVs40 V4. 40 …”

Section: Methodsmentioning

confidence: 99%

The Aspergillus nidulans Proline Permease as a Model for Understanding the Factors Determining Substrate Binding and Specificity of Fungal Amino Acid Transporters

Gournas

Evangelidis

Αθανασόπουλος

et al. 2015

Journal of Biological Chemistry

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Background: PrnB, different from Put4p, its Saccharomyces cerevisiae orthologue, is a highly specific L-proline transporter of Aspergillus nidulans. Results: Identification of 12 residues important for PrnB activity and/or specificity. Put4p-mimicking mutants of PrnB recognize other Put4p substrates. Conclusion: Residues variable in the yeast amino acid transporter (YAT) family determine transporter specificity. Significance: Understanding the molecular mechanisms underlying amino acid recognition and translocation through YATs.

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TOPCONS: consensus prediction of membrane protein topology

Cited by 500 publications

References 19 publications

Differential regulation of staphylococcal virulence by the sensor kinase SaeS in response to neutrophil-derived stimuli

Differential regulation of staphylococcal virulence by the sensor kinase SaeS in response to neutrophil-derived stimuli

A Novel Zinc Binding System, ZevAB, Is Critical for Survival of Nontypeable Haemophilus influenzae in a Murine Lung Infection Model

The Aspergillus nidulans Proline Permease as a Model for Understanding the Factors Determining Substrate Binding and Specificity of Fungal Amino Acid Transporters

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