Prediction of twin-arginine signal peptides

BackgroundProteins 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.ResultsWe 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.ConclusionThe 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 http://www.cbs.dtu.dk/services/TatP/.

[1]  H. Bernstein,et al.  The targeting pathway of Escherichia coli presecretory and integral membrane proteins is specified by the hydrophobicity of the targeting signal , 2001, Proceedings of the National Academy of Sciences of the United States of America.

[2]  B. Berks,et al.  Overlapping functions of components of a bacterial Sec‐independent protein export pathway , 1998, The EMBO journal.

[3]  T. Silhavy,et al.  Secretion of LamB-LacZ by the Signal Recognition Particle Pathway of Escherichia coli , 2003, Journal of bacteriology.

[4]  Frank Sargent,et al.  The Tat protein translocation pathway and its role in microbial physiology. , 2003, Advances in microbial physiology.

[5]  Zoya Ignatova,et al.  Unusual signal peptide directs penicillin amidase from Escherichia coli to the Tat translocation machinery. , 2002, Biochemical and biophysical research communications.

[6]  Rolf Apweiler,et al.  The SWISS-PROT protein sequence data bank and its supplement TrEMBL , 1997, Nucleic Acids Res..

[7]  Frank Sargent,et al.  Behaviour of topological marker proteins targeted to the Tat protein transport pathway , 2002, Molecular microbiology.

[8]  Gunnar von Heijne,et al.  Competition between Sec‐ and TAT‐dependent protein translocation in Escherichia coli , 1999, The EMBO journal.

[9]  Romé Voulhoux,et al.  In vivo dissection of the Tat translocation pathway in Escherichia coli. , 2002, Journal of molecular biology.

[10]  Frens Pries,et al.  Selective Contribution of the Twin-Arginine Translocation Pathway to Protein Secretion in Bacillus subtilis * , 2002, The Journal of Biological Chemistry.

[11]  G von Heijne,et al.  Topological Rules for Membrane Protein Assembly in Eukaryotic Cells* , 1997, The Journal of Biological Chemistry.

[12]  S M Musser,et al.  Characterization of the early steps of OE17 precursor transport by the thylakoid DeltapH/Tat machinery. , 2000, European journal of biochemistry.

[13]  W. Wickner,et al.  Functional reconstitution of bacterial Tat translocation in vitro , 2001, The EMBO journal.

[14]  B. Berks A common export pathway for proteins binding complex redox cofactors? , 1996, Molecular microbiology.

[15]  Rolf Apweiler,et al.  The SWISS-PROT protein sequence database and its supplement TrEMBL in 2000 , 2000, Nucleic Acids Res..

[16]  S. Brunak,et al.  SHORT COMMUNICATION Identification of prokaryotic and eukaryotic signal peptides and prediction of their cleavage sites , 1997 .

[17]  George Georgiou,et al.  Genetic Analysis of the Twin Arginine Translocator Secretion Pathway in Bacteria* , 2002, The Journal of Biological Chemistry.

[18]  T. D. Schneider,et al.  Sequence logos: a new way to display consensus sequences. , 1990, Nucleic acids research.

[19]  J. Weiner,et al.  A Novel and Ubiquitous System for Membrane Targeting and Secretion of Cofactor-Containing Proteins , 1998, Cell.

[20]  Jessica C Kissinger,et al.  Adaptation of protein secretion to extremely high‐salt conditions by extensive use of the twin‐arginine translocation pathway , 2002, Molecular microbiology.

[21]  Søren Brunak,et al.  A Neural Network Method for Identification of Prokaryotic and Eukaryotic Signal Peptides and Prediction of their Cleavage Sites , 1997, Int. J. Neural Syst..

[22]  R. Herrmann,et al.  A new type of signal peptide: central role of a twin‐arginine motif in transfer signals for the delta pH‐dependent thylakoidal protein translocase. , 1995, The EMBO journal.

[23]  E. Hartmann,et al.  Prokaryotic Utilization of the Twin-Arginine Translocation Pathway: a Genomic Survey , 2003, Journal of bacteriology.

[24]  George Georgiou,et al.  Folding quality control in the export of proteins by the bacterial twin-arginine translocation pathway , 2003, Proceedings of the National Academy of Sciences of the United States of America.

[25]  Sierd Bron,et al.  Two minimal Tat translocases in Bacillus , 2004, Molecular microbiology.

[26]  R. Herrmann,et al.  The Rieske Fe/S protein of the cytochrome b6/f complex in chloroplasts: missing link in the evolution of protein transport pathways in chloroplasts? , 2001, The Journal of biological chemistry.

[27]  B. Berks,et al.  The Twin Arginine Consensus Motif of Tat Signal Peptides Is Involved in Sec-independent Protein Targeting in Escherichia coli * , 2000, The Journal of Biological Chemistry.

[28]  B. Berks,et al.  A naturally occurring bacterial Tat signal peptide lacking one of the ‘invariant’ arginine residues of the consensus targeting motif , 2001, FEBS letters.

[29]  S. Brunak,et al.  Improved prediction of signal peptides: SignalP 3.0. , 2004, Journal of molecular biology.

[30]  Frank Sargent,et al.  A genetic screen for suppressors of Escherichia coli Tat signal peptide mutations establishes a critical role for the second arginine within the twin-arginine motif , 2001, Archives of Microbiology.