Abstract
The recently published 3D-footprint database contains an up-to-date repository of protein-DNA complexes of known structure that belong to different superfamilies and bind to DNA with distinct specificities. This repository can be scanned by means of sequence alignments in order to look for similar DNA-binding proteins, which might in turn recognize similar DNA motifs. Here we take the complete set of Homeobox proteins from Drosophila melanogaster and their preferred DNA motifs, which would fall in the largest 3D-footprint superfamily and were recently characterized by Noyes and collaborators, and annotate their interface residues. We then analyze the observed amino acid substitutions at equivalent interface positions and their effect on recognition. Finally we estimate to what extent interface similarity, computed over the set of residues which mediate DNA recognition, outperforms BLAST expectation values when deciding whether two aligned Homeobox proteins might bind to the same DNA motif.
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References
Contreras-Moreira, B.: 3D-footprint: a database for the structural analysis of protein-DNA complexes. Nucleic Acids Res. 38(Database issue), D91–D97 (2010)
Berman, H.M., Westbrook, J., Feng, Z., Gilliland, G., Bhat, T.N., Weissig, H., Shindyalov, I.N., Bourne, P.E.: The Protein Data Bank. Nucleic Acids Res. 28(1), 235–242 (2000)
Murzin, A.G., Brenner, S.E., Hubbard, T., Chothia, C.: SCOP: a structural classification of proteins database for the investigation of sequences and structures. J. Mol. Biol. 247, 536–540 (1995)
Lewis, E.B.: A gene complex controlling segmentation in Drosophila. Nature 276, 565–570 (1978)
Noyes, M.B., Christensen, R.G., Wakabayashi, A., Stormo, G.D., Brodsky, M.H., Wolfe, S.A.: Analysis of homeodomain specificities allows the family-wide prediction of preferred recognition sites. Cell 133, 1277–1289 (2008)
Hertz, G.Z., Stormo, G.D.: Identifying DNA and protein patterns with statistically significant alignments of multiple sequences. Bioinformatics 15, 563–577 (1999)
Bailey, T.L., Williams, N., Misleh, C., Li, W.W.: MEME: discovering and analyzing DNA and protein sequence motifs. Nucleic Acids Res. 34, W369–W373 (2006)
Altschul, S.F., Gish, W., Miller, W., Myers, E.W., Lipman, D.J.: Basic local alignment search tool. J. Mol. Biol. 215, 403–410 (1990)
Mahony, S., Benos, P.V.: STAMP: a web tool for exploring DNA-binding motif similarities. Nucleic Acids Res. 35, W253–W258 (2007)
Contreras-Moreira, B., Sancho, J., Espinosa Angarica, V.: Comparison of DNA binding across protein superfamilies. Proteins 78(1), 52–62 (2009)
Edgar, R.C.: MUSCLE: multiple sequence alignment with high accuracy and high throughput. Nucleic Acids Res. 32, 1792–1797 (2004)
Henikoff, S., Henikoff, J.G.: Amino acid substitution matrices from protein blocks. Proc. Natl. Acad. Sci. 89, 10915–10919 (1992)
R Development Core Team: R: A Language and Environment for Statistical Computing. R Foundation for Statistical Computing, Vienna, Austria (2009)
Wingender, E., Dietze, P., Karas, H., Knuppel, R.: TRANSFAC: a database on transcription factors and their DNA binding sites. Nucleic Acids Res. 24, 238–241 (1996)
Berger, M.F., Badis, G., Gehrke, A.R., Talukder, S., Philippakis, A.A., Peña-Castillo, L., Alleyne, T.M., Mnaimneh, S., Botvinnik, O.B., Chan, E.T., Khalid, F., Zhang, W., Newburger, D., Jaeger, S.A., Morris, Q.D., Bulyk, M.L., Hughes, T.R.: Variation in Homeodomain DNA Binding Revealed by High-Resolution Analysis of Sequence Preferences. Cell 133(7), 1266–1276 (2008)
Luscombe, N.M., Thornton, J.M.: Protein-DNA interactions: amino acid conservation and the effects of mutations on binding specificity. J. Mol. Biol. 320(5), 991–1009 (2002)
Morozov, A.V., Siggia, E.D.: Connecting protein structure with predictions of regulatory sites. Proc. Natl. Acad. Sci. 104, 7068–7073 (2007)
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Sebastián, Á., P. Cantalapiedra, C., Contreras-Moreira, B. (2012). Interface Similarity Improves Comparison of DNA-Binding Proteins: The Homeobox Example. In: Freitas, A.T., Navarro, A. (eds) Bioinformatics for Personalized Medicine. JBI 2010. Lecture Notes in Computer Science(), vol 6620. Springer, Berlin, Heidelberg. https://doi.org/10.1007/978-3-642-28062-7_8
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DOI: https://doi.org/10.1007/978-3-642-28062-7_8
Publisher Name: Springer, Berlin, Heidelberg
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