Abstract
Gram-positive bacteria have surface proteins that are often implicated in virulence. A group of extracellular proteins attached to the cell wall contains an LPXTG-like motif that is target for cleavage and covalent coupling to peptidoglycan by sortase enzymes. A Hidden Markov Model (HMM) was developed for predicting the LPXTG and LPXTG-like cell-wall proteins of Gram-positive bacteria. The model is the first capable of predicting alternative (i.e. other than LPXTG-containing) substrates. Our analysis of 177 completely sequenced genomes identified 1456 cell-wall proteins, a number larger compared to the previously available methods. Among these, apart from the previously identified 1283 proteins carrying the LPXTG motif, we identified 39 newly identified proteins carrying NPXTG, 53 carrying LPXTA and 81 carrying the LAXTG motif. The tool is freely available for academic use at http://bioinformatics.biol.uoa.gr/CW-PRED/ .
This is a preview of subscription content, log in via an institution to check access.
Access this chapter
Tax calculation will be finalised at checkout
Purchases are for personal use only
Preview
Unable to display preview. Download preview PDF.
References
Lee, S.G., Pancholi, V., Fischetti, V.A.: Characterization of a unique glycosylated anchor endopeptidase that cleaves the LPXTG sequence motif of cell surface proteins of Gram-positive bacteria. J. Biol. Chem. 277, 46912–46922 (2002)
Cabanes, D., Dehoux, P., Dussurget, O., Frangeul, L., Cossart, P.: Surface proteins and the pathogenic potential of Listeria monocytogenes. Trends Microbiol. 10, 238–245 (2002)
Navarre, W.W., Schneewind, O.: Surface proteins of gram-positive bacteria and mechanisms of their targeting to the cell wall envelope. Microbiol. Mol. Biol. Rev. 63, 174–229 (1999)
Fischetti, V.A., Pancholi, V., Schneewind, O.: Conservation of a hexapeptide sequence in the anchor region of surface proteins from gram-positive cocci. Mol. Microbiol. 4, 1603–1605 (1990)
Marraffini, L.A., Dedent, A.C., Schneewind, O.: Sortases and the art of anchoring proteins to the envelopes of gram-positive bacteria. Microbiol. Mol. Biol. Rev. 70, 192–221 (2006)
Roche, F.M., Massey, R., Peacock, S.J., Day, N.P., Visai, L., Speziale, P., Lam, A., Pallen, M., Foster, T.J.: Characterization of novel LPXTG-containing proteins of Staphylococcus aureus identified from genome sequences. Microbiology 149, 643–654 (2003)
Guttilla, I.K., Gaspar, A.H., Swierczynski, A., Swaminathan, A., Dwivedi, P., Das, A., Ton-That, H.: Acyl enzyme intermediates in sortase-catalyzed pilus morphogenesis in gram-positive bacteria. J. Bacteriol. 191, 5603–5612 (2009)
Mazmanian, S.K., Ton-That, H., Su, K., Schneewind, O.: An iron-regulated sortase anchors a class of surface protein during Staphylococcus aureus pathogenesis. Proc. Natl. Acad. Sci. U S A 99, 2293–2298 (2002)
Ton-That, H., Mazmanian, S.K., Faull, K.F., Schneewind, O.: Anchoring of surface proteins to the cell wall of Staphylococcus aureus. Sortase catalyzed in vitro transpeptidation reaction using LPXTG peptide and NH(2)-Gly(3) substrates. J. Biol. Chem. 275, 9876–9881 (2000)
Marraffini, L.A., Schneewind, O.: Targeting proteins to the cell wall of sporulating Bacillus anthracis. Mol. Microbiol. 62, 1402–1417 (2006)
Maresso, A.W., Schneewind, O.: Sortase as a target of anti-infective therapy. Pharmacol. Rev. 60, 128–141 (2008)
Ton-That, H., Marraffini, L.A., Schneewind, O.: Protein sorting to the cell wall envelope of Gram-positive bacteria. Biochim. Biophys. Acta 1694, 269–278 (2004)
Zhou, M., Boekhorst, J., Francke, C., Siezen, R.J.: LocateP: genome-scale subcellular-location predictor for bacterial proteins. BMC Bioinformatics 9, 173 (2008)
Boekhorst, J., de Been, M.W., Kleerebezem, M., Siezen, R.J.: Genome-wide detection and analysis of cell wall-bound proteins with LPxTG-like sorting motifs. J. Bacteriol. 187, 4928–4934 (2005)
Litou, Z.I., Bagos, P.G., Tsirigos, K.D., Liakopoulos, T.D., Hamodrakas, S.J.: Prediction of cell wall sorting signals in gram-positive bacteria with a hidden markov model: application to complete genomes. J. Bioinform. Comput. Biol. 6, 387–401 (2008)
Hobohm, U., Scharf, M., Schneider, R., Sander, C.: Selection of representative protein data sets. Protein Science: A Publication of the Protein Society 1, 409–417 (1992)
Wu, C.H., Apweiler, R., Bairoch, A., Natale, D.A., Barker, W.C., Boeckmann, B., Ferro, S., Gasteiger, E., Huang, H., Lopez, R., Magrane, M., Martin, M.J., Mazumder, R., O’Donovan, C., Redaschi, N., Suzek, B.: The Universal Protein Resource (UniProt): an expanding universe of protein information. Nucleic Acids Res. 34, D187–D191 (2006)
Comfort, D., Clubb, R.T.: A comparative genome analysis identifies distinct sorting pathways in gram-positive bacteria. Infect Immun. 72, 2710–2722 (2004)
Davies, J.R., Svensater, G., Herzberg, M.C.: Identification of novel LPXTG-linked surface proteins from Streptococcus gordonii. Microbiology 155, 1977–1988 (2009)
Egan, S.A., Kurian, D., Ward, P.N., Hunt, L., Leigh, J.A.: Identification of sortase A (SrtA) substrates in Streptococcus uberis: evidence for an additional hexapeptide (LPXXXD) sorting motif. J. Proteome Res. 9, 1088–1095 (2010)
Author information
Authors and Affiliations
Editor information
Editors and Affiliations
Rights and permissions
Copyright information
© 2012 Springer-Verlag Berlin Heidelberg
About this paper
Cite this paper
Fimereli, D.K., Tsirigos, K.D., Litou, Z.I., Liakopoulos, T.D., Bagos, P.G., Hamodrakas, S.J. (2012). CW-PRED: A HMM-Based Method for the Classification of Cell Wall-Anchored Proteins of Gram-Positive Bacteria. In: Maglogiannis, I., Plagianakos, V., Vlahavas, I. (eds) Artificial Intelligence: Theories and Applications. SETN 2012. Lecture Notes in Computer Science(), vol 7297. Springer, Berlin, Heidelberg. https://doi.org/10.1007/978-3-642-30448-4_36
Download citation
DOI: https://doi.org/10.1007/978-3-642-30448-4_36
Publisher Name: Springer, Berlin, Heidelberg
Print ISBN: 978-3-642-30447-7
Online ISBN: 978-3-642-30448-4
eBook Packages: Computer ScienceComputer Science (R0)