TM or not TM: transmembrane protein prediction with low false positive rate using DAS-TMfilter

Cserző, Miklós; Eisenhaber, Frank; Eisenhaber, Birgit; Simon, István

doi:10.1093/bioinformatics/btg394

Cited by 93 publications

(65 citation statements)

References 7 publications

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“…BepE and BepG also showed considerable identity to the aromatic hydrocarbon TtgB transporter (56) from Pseudomonas putida (43 and 37%, respectively) and the broad-spectrum CmeB RND efflux pump (34) from Campylobacter jejuni (51 and 38%). Sequence analysis using the DAS server (14) revealed that BepE and BepG possess the classical pattern of an RND transporter (15) with 12 hydrophobic transmembrane segments (TMS) and two large loops (ϳ300 amino acids) between TMS 1 and 2 and TMS 7 and 8. Multiple alignments of B. suis BepE and BepG with the MexB and AcrB RND proteins also showed the characteristic pattern of the RND family described by Putman et al (55), with high levels of amino acid conservation between the Bep proteins and AcrB and MexB (Fig.…”

Section: Resultsmentioning

confidence: 99%

Interplay between Two RND Systems Mediating Antimicrobial Resistance inBrucella suis

Martín

Posadas

Carrica³

et al. 2009

J Bacteriol

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The RND-type efflux pumps are responsible for the multidrug resistance phenotype observed in many clinically relevant species. Also, RND pumps have been implicated in physiological processes, with roles in the virulence mechanisms of several pathogenic bacteria. We have previously shown that the BepC outer membrane factor of Brucella suis is involved in the efflux of diverse drugs, probably as part of a tripartite complex with an inner membrane translocase. In the present work, we characterize two membrane fusion protein-RND translocases of B. suis encoded by the bepDE and bepFG loci. MIC assays showed that the B. suis ⌬bepE mutant was more sensitive to deoxycholate (DOC), ethidium bromide, and crystal violet. Furthermore, multicopy bepDE increased resistance to DOC and crystal violet and also to other drugs, including ampicillin, norfloxacin, ciprofloxacin, tetracycline, and doxycycline. In contrast to the ⌬bepE mutant, the resistance profile of B. suis remained unaltered when the other RND gene (bepG) was deleted. However, the ⌬bepE ⌬bepG double mutant showed a more severe phenotype than the ⌬bepE mutant, indicating that BepFG also contributes to drug resistance. An open reading frame (bepR) coding for a putative regulatory protein of the TetR family was found upstream of the bepDE locus. BepR strongly repressed the activity of the bepDE promoter, but DOC released the repression mediated by BepR. A clear induction of the bepFG promoter activity was observed only in the BepDE-defective mutant, indicating a regulatory interplay between the two RND efflux pumps. Although only the BepFG-defective mutant showed a moderate attenuation in model cells, the activities of both bepDE and bepFG promoters were induced in the intracellular environment of HeLa cells. Our results show that B. suis harbors two functional RND efflux pumps that may contribute to virulence.Brucella is a facultative intracellular pathogen taxonomically classified within the Alphaproteobacteria, along with other intracellular pathogens, such as Rickettsia, Bartonella, and several plant symbionts and pathogens (7). Brucella spp. are the etiological agents of brucellosis, a major zoonotic disease distributed worldwide and transmitted from domestic, farm, and wild animals to humans. Brucella enters the host through the nasal, oral, and pharyngeal cavities and from there is transported to the proximal lymph nodes. Early during infection, host innate immunity mechanisms contribute to reduce the initial number of infecting brucellae (26). Once in contact with the organism, Brucella is able to invade professional and nonprofessional phagocytes (10). Within the cells, Brucella is found in a membrane-associated vacuole called a Brucellacontaining vacuole. The Brucella-containing vacuole is able to subvert the normal phagocytic pathway to form a vacuole with endoplasmic reticulum markers suitable for Brucella sp. replication (13,50). This strategy helps the bacteria to escape from the bactericidal mechanisms used by the host (7).Host barriers range from anti...

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Section: Resultsmentioning

confidence: 99%

Interplay between Two RND Systems Mediating Antimicrobial Resistance inBrucella suis

Martín

Posadas

Carrica³

et al. 2009

J Bacteriol

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“…Protein motifs and pattern searches were performed using SMART [http://smart.embl-heidelberg.de/ (Letunic et al, 2004;Schultz et al, 1998)], CDD (http://www.ncbi.nlm.nih.gov/; NCBI) and PSORT II (http://psort.nibb.ac.jp/form2.html). Transmembrane domains were calculated using the membrane protein topology database [http://blanco.biomol.uci.edu/mptopo/ (Jayasinghe et al, 2001)], the TMHMM 2.0 prediction software [http://www.cbs.dtu.dk/ services/TMHMM/ (Krogh et al, 2001)], the SOSUI system (http://sosui.proteome.bio.tuat.ac.jp/) and the DAS-TM filter algorithm (Cserzo et al, 2004). Phylogenetic tree predictions were done using eSHADOW [http://eshadow.dcode.org/ (Ovcharenko et al, 2004)] and visualized using the Phylodendron software (http://iubio.bio.indiana.edu/treeapp/).…”

Section: Electron Microscopymentioning

confidence: 99%

LEM2 is a novel MAN1-related inner nuclear membrane protein associated with A-type lamins

Brachner

Reipert

Foisner

et al. 2005

Journal of Cell Science

131

135

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The LEM (lamina-associated polypeptide–emerin–MAN1) domain is a motif shared by a group of lamin-interacting proteins in the inner nuclear membrane (INM) and in the nucleoplasm. The LEM domain mediates binding to a DNA-crosslinking protein, barrier-to-autointegration factor (BAF). We describe a novel, ubiquitously expressed LEM domain protein, LEM2, which is structurally related to MAN1. LEM2 contains an N-terminal LEM motif, two predicted transmembrane domains and a MAN1-Src1p C-terminal (MSC) domain highly homologous to MAN1, but lacks the MAN1-specific C-terminal RNA-recognition motif. Immunofluorescence microscopy of digitonin-treated cells and subcellular fractionation identified LEM2 as a lamina-associated protein residing in the INM. LEM2 binds to the lamin C tail in vitro. Targeting of LEM2 to the nuclear envelope requires A-type lamins and is mediated by the N-terminal and transmembrane domains. Highly overexpressed LEM2 accumulates in patches at the nuclear envelope and forms membrane bridges between nuclei of adjacent cells. LEM2 structures recruit A-type lamins, emerin, MAN1 and BAF, whereas lamin B and lamin B receptor are excluded. Our data identify LEM2 as a novel A-type-lamin-associated INM protein involved in nuclear structure organization.

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“…Intrinsic disorder was estimated using the IUPred (Dosztányi 2005), RONN (Yang 2005) and VSL2B (Obradovic 2005) algorithms, transmembrane helix forming propensity using DAS-TMfilter (Cserző 2004), TMHMM (Krogh 2001) and PHOBIUS (Käll 2004) and aggregation propensity using FoldAmyloid (Garbuzynskiy 2010) and the TANGO/WALTZ (Fernandez-Escamilla 2004;Maurer-Stroh 2010) algorithms. None of these predictors use evolutionary information during data processing, thus we expect that they can be used for de novo sequences in an unbiased way.…”

Section: Methodsmentioning

confidence: 99%

Are Proposed Early Genetic Codes Capable of Encoding Viable Proteins?

2014

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Proteins are elaborate biopolymers balancing between contradicting intrinsic propensities to fold, aggregate or remain disordered. Assessing their primary structural preferences observable without evolutionary optimization has been reinforced by the recent identification of de novo proteins that have emerged from previously non-coding sequences. In this paper we investigate structural preferences of hypothetical proteins translated from random DNA segments using the standard genetic code and three of its proposed evolutionarily predecessor models encoding 10, 6 and 4 amino acids, respectively. Our only main assumption is that the disorder, aggregation and transmembrane helix predictions used are able to reflect the differences in the trends of the protein sets investigated. We found that the 10-residue code encodes proteins that resemble modern proteins in their predicted structural properties. All of the investigated early genetic codes give rise to proteins with enhanced disorder and diminished aggregation propensities. Our results suggest that an ancestral genetic code similar to the proposed 10-residue one is capable of encoding functionally diverse proteins but these might have existed under conditions different from today's common physiological ones. The existence of a protein functional repertoire for the investigated earlier stages which is quite distinct as it is today can be deduced from the presented results.

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TM or not TM: transmembrane protein prediction with low false positive rate using DAS-TMfilter

Abstract: The server operates at three mirror sites: http://mendel.imp.univie.ac.at/sat/DAS/DAS.html, http://wooster.bip.bham.ac.uk/DAS.html and http://www.enzim.hu/DAS/DAS.html. The program is available on request.

Cited by 93 publications

References 7 publications

Interplay between Two RND Systems Mediating Antimicrobial Resistance inBrucella suis

Interplay between Two RND Systems Mediating Antimicrobial Resistance inBrucella suis

LEM2 is a novel MAN1-related inner nuclear membrane protein associated with A-type lamins

Are Proposed Early Genetic Codes Capable of Encoding Viable Proteins?

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