Prediction of twin-arginine signal peptides.

Center for Biological Sequence Analysis, BioCentrum-DTU, Technical University of Denmark, Building 208, DK-2800, Lyngby, Denmark.
BMC Bioinformatics (Impact Factor: 2.67). 02/2005; 6:167. DOI: 10.1186/1471-2105-6-167
Source: PubMed

ABSTRACT Proteins carrying twin-arginine (Tat) signal peptides are exported into the periplasmic compartment or extracellular environment independently of the classical Sec-dependent translocation pathway. To complement other methods for classical signal peptide prediction we here present a publicly available method, TatP, for prediction of bacterial Tat signal peptides.
We have retrieved sequence data for Tat substrates in order to train a computational method for discrimination of Sec and Tat signal peptides. The TatP method is able to positively classify 91% of 35 known Tat signal peptides and 84% of the annotated cleavage sites of these Tat signal peptides were correctly predicted. This method generates far less false positive predictions on various datasets than using simple pattern matching. Moreover, on the same datasets TatP generates less false positive predictions than a complementary rule based prediction method.
The method developed here is able to discriminate Tat signal peptides from cytoplasmic proteins carrying a similar motif, as well as from Sec signal peptides, with high accuracy. The method allows filtering of input sequences based on Perl syntax regular expressions, whereas hydrophobicity discrimination of Tat- and Sec-signal peptides is carried out by an artificial neural network. A potential cleavage site of the predicted Tat signal peptide is also reported. The TatP prediction server is available as a public web server at

1 Bookmark
  • [Show abstract] [Hide abstract]
    ABSTRACT: The genus Rickettsia (Alphaproteobacteria; Rickettsiales; Rickettsiaceae) is comprised of obligate intracellular parasites, with virulent species of interest both as causes of emerging infectious diseases and for their potential deployment as bioterrorism agents. Currently there are no effective commercially available vaccines, with treatment limited primarily to tetracycline antibiotics, though others (e.g., josamycin, ciprofloxacin, chloramphenicol and azithromycin) are also effective. Much of the recent research geared towards understanding mechanisms underlying rickettsial pathogenicity has centered on characterization of secreted proteins that directly engage eukaryotic cells. Herein, we review all aspects of the Rickettsia secretome, including six secretion systems, 19 characterized secretory proteins, and potential moonlighting proteins identified on surfaces of multiple Rickettsia species. Employing bioinformatics and phylogenomics, we present novel structural and functional insight on each secretion system. Unexpectedly, our investigation revealed that the majority of characterized secretory proteins have not been assigned to their cognate secretion pathways. Furthermore, for most secretion pathways, the requisite signal sequences mediating translocation are poorly understood. As a blueprint for all known routes of protein translocation into host cells, this resource will assist research aimed at uniting characterized secreted proteins with their apposite secretion pathways. Furthermore, our work will help in the identification of novel secreted proteins involved in rickettsial “life on the inside”.This article is protected by copyright. All rights reserved.
    FEMS microbiology reviews 08/2014; · 13.81 Impact Factor
  • Source
    [Show abstract] [Hide abstract]
    ABSTRACT: Soon after synthesis, proteins are transported to their respective destinations to perform various cellular activities needed for the survival of the cell. Protein trafficking is a complex process. In prokaryotes, 16 different mechanisms are involved in transporting the proteins to their respective destinations. Interestingly, except one, the rest of them transport unfolded pro-teins. A number of proteins acquire folded conforma-tion before targeting/transporting across membranes. Such prefolded proteins are transported through a novel pathway, known as twin arginine transport (Tat) pathway. The Tat pathway is found in both Gram-positive as well as Gram-negative bacteria and plays a key role in various cellular activities including pathogenesis. The review provides a comprehensive picture of the mechanism of the Tat pathway and describes its role in pathogenesis. BACTERIA need to transport proteins across their membrane to have constant interaction with their extracellular mi-lieu. While struggling to survive in harsh environment, they have designed a number of mechanisms to send cer-tain proteins across/into the membranes. These proteins perform important functions such as cell envelope bio-genesis, nutrient acquisition, motility, cell to cell com-munication, etc. and play a key role in cell viability 1 . In prokaryotes, about 16 distinct protein transport systems are known to contribute towards translocation/targeting of proteins across/into the membranes. Some of them, such as T4S, T4P, TAT, Sec, Yidc are found operational in both Gram-negative and Gram-positive bacteria, whereas the other transport systems are found exclusively either in Gram-negative (T6S, Fla, T3S, Cu, T2S, LOL, T5S, TPS and Omp85) or in Gram-positive (Sort and Esx) bacte-ria 2,3 . Most of the extracellular proteins acquire functional conformation only after reaching their destination. How-ever, certain proteins can acquire folded conformation only in the cytoplasm. The periplasmic or extracellular environment, due to a variety of reasons, is unsuitable for their folding. These include (i) dependence of proteins on large cofactors for activity 4,5 ; (ii) acquisition of folded conformation while they are still in cytoplasm 6 ; (iii) un-favourable extracellular environment, such as high tem-perature, salt concentration, etc. for folding; (iv) failure to fold in a relatively more oxidizing environment prevail-ing in periplasmic space of Gram-negative bacteria 4 and (v) multi-subunit protein complexes 6 . However, folded conformation acts as a structural hinderance for using the conventional protein transport pathways evolved exclu-sively for transport of unfolded proteins. Such a complex task of transporting/targeting of prefolded proteins across the hydrophobic phospholipid bilayer, without damaging its integrity, is operated through unique protein translo-cases and chaperones. In addition to these two require-ments, unique structural features found in the signal peptides of prefolded proteins contribute towards chaper-one-specific interactions through a novel mechanism known as Sec-avoidance 7 . A signature sequence motif with twin arginines are found in the N-terminal positive region and it is shown to be essential for membrane tar-geting/transport of all prefolded proteins. Therefore, the unique transport pathway is named as twin arginine transport (Tat) pathway. Originally, the Tat pathway was discovered in plants while studying the transport of nuclear genome coded proteins to the thylakoid mem-brane 8,9 . Later, Weiner et al. have shown its existence in Escherichia coli while unravelling the mechanism of membrane targeting of redox proteins, such as nitrate reductase (NapA), trimethylamine N-oxide reductase (TorA) and molybdoenzyme dimethyl sulphoxide reduc-tase (DmsABC) 10,11 . Since then, a number of Tat sub-strates were shown to exist both in Gram-negative and Gram-positive bacteria. A few examples are shown in Table 1. Initially the Tat pathway is assumed to have exclusively evolved to transport/target proteins contain-ing large cofactors. However, in recent times a number of cofactor-less proteins or proteins with small cofactors are shown to take Tat route for targeting/translocating across the membrane 4,12 . The focus of this review is to high-light the mechanism of transport and its role in patho-genesis.
  • Source
    [Show abstract] [Hide abstract]
    ABSTRACT: The Gram-negative methanotroph Methylococcus capsulatus (Bath) was recently demonstrated to abrogate inflammation in a murine model of inflammatory bowel disease, suggesting interactions with cells involved in maintaining mucosal homeostasis and emphasizing the importance of understanding the many properties of M. capsulatus. Secreted proteins determine how bacteria may interact with their environment, and a comprehensive knowledge of such proteins is therefore vital to understand bacterial physiology and behavior. The aim of this study was to systematically analyze protein secretion in M. capsulatus (Bath) by identifying the secretion systems present and the respective secreted substrates. Computational analysis revealed that in addition to previously recognized type II secretion systems and a type VII secretion system, a type Vb (two-partner) secretion system and putative type I secretion systems are present in M. capsulatus (Bath). In silico analysis suggests that the diverse secretion systems in M.capsulatus transport proteins likely to be involved in adhesion, colonization, nutrient acquisition and homeostasis maintenance. Results of the computational analysis was verified and extended by an experimental approach showing that in addition an uncharacterized protein and putative moonlighting proteins are released to the medium during exponential growth of M. capsulatus (Bath).
    PLoS ONE 12/2014; 9(12):e114476. · 3.53 Impact Factor

Full-text (2 Sources)

Available from
May 19, 2014