References of "Contreras-Moreira, Bruno"
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See detailComparison of DNA binding across protein superfamilies.
Contreras-Moreira, Bruno; Sancho, Javier; Espinosa Angarica, Vladimir UL

in Proteins (2010), 78(1), 52-62

Specific protein-DNA interactions are central to a wide group of processes in the cell and have been studied both experimentally and computationally over the years. Despite the increasing collection of ... [more ▼]

Specific protein-DNA interactions are central to a wide group of processes in the cell and have been studied both experimentally and computationally over the years. Despite the increasing collection of protein-DNA complexes, so far only a few studies have aimed at dissecting the structural characteristics of DNA binding among evolutionarily related proteins. Some questions that remain to be answered are: (a) what is the contribution of the different readout mechanisms in members of a given structural superfamily, (b) what is the degree of interface similarity among superfamily members and how this affects binding specificity, (c) how DNA-binding protein superfamilies distribute across taxa, and (d) is there a general or family-specific code for the recognition of DNA. We have recently developed a straightforward method to dissect the interface of protein-DNA complexes at the atomic level and here we apply it to study 175 proteins belonging to nine representative superfamilies. Our results indicate that evolutionarily unrelated DNA-binding domains broadly conserve specificity statistics, such as the ratio of indirect/direct readout and the frequency of atomic interactions, therefore supporting the existence of a set of recognition rules. It is also found that interface conservation follows trends that are superfamily-specific. Finally, this article identifies tendencies in the phylogenetic distribution of transcription factors, which might be related to the evolution of regulatory networks, and postulates that the modular nature of zinc finger proteins can explain its role in large genomes, as it allows for larger binding interfaces in a single protein molecule. [less ▲]

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See detailPrediction of TF target sites based on atomistic models of protein-DNA complexes.
Espinosa Angarica, Vladimir UL; Perez, Abel Gonzalez; Vasconcelos, Ana T. et al

in BMC bioinformatics (2008), 9

BACKGROUND: The specific recognition of genomic cis-regulatory elements by transcription factors (TFs) plays an essential role in the regulation of coordinated gene expression. Studying the mechanisms ... [more ▼]

BACKGROUND: The specific recognition of genomic cis-regulatory elements by transcription factors (TFs) plays an essential role in the regulation of coordinated gene expression. Studying the mechanisms determining binding specificity in protein-DNA interactions is thus an important goal. Most current approaches for modeling TF specific recognition rely on the knowledge of large sets of cognate target sites and consider only the information contained in their primary sequence. RESULTS: Here we describe a structure-based methodology for predicting sequence motifs starting from the coordinates of a TF-DNA complex. Our algorithm combines information regarding the direct and indirect readout of DNA into an atomistic statistical model, which is used to estimate the interaction potential. We first measure the ability of our method to correctly estimate the binding specificities of eight prokaryotic and eukaryotic TFs that belong to different structural superfamilies. Secondly, the method is applied to two homology models, finding that sampling of interface side-chain rotamers remarkably improves the results. Thirdly, the algorithm is compared with a reference structural method based on contact counts, obtaining comparable predictions for the experimental complexes and more accurate sequence motifs for the homology models. CONCLUSION: Our results demonstrate that atomic-detail structural information can be feasibly used to predict TF binding sites. The computational method presented here is universal and might be applied to other systems involving protein-DNA recognition. [less ▲]

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See detailThe role of DNA-binding specificity in the evolution of bacterial regulatory networks.
Lozada-Chavez, Irma; Espinosa Angarica, Vladimir UL; Collado-Vides, Julio et al

in Journal of molecular biology (2008), 379(3), 627-43

Understanding the mechanisms by which transcriptional regulatory networks (TRNs) change through evolution is a fundamental problem.Here, we analyze this question using data from Escherichia coli and ... [more ▼]

Understanding the mechanisms by which transcriptional regulatory networks (TRNs) change through evolution is a fundamental problem.Here, we analyze this question using data from Escherichia coli and Bacillus subtilis, and find that paralogy relationships are insufficient to explain the global or local role observed for transcription factors (TFs) within regulatory networks. Our results provide a picture in which DNA-binding specificity, a molecular property that can be measured in different ways, is a predictor of the role of transcription factors. In particular, we observe that global regulators consistently display low levels of binding specificity, while displaying comparatively higher expression values in microarray experiments. In addition, we find a strong negative correlation between binding specificity and the number of co-regulators that help coordinate genetic expression on a genomic scale. A close look at several orthologous TFs,including FNR, a regulator found to be global in E. coli and local in B.subtilis, confirms the diagnostic value of specificity in order to understand their regulatory function, and highlights the importance of evaluating the metabolic and ecological relevance of effectors as another variable in the evolutionary equation of regulatory networks. Finally, a general model is presented that integrates some evolutionary forces and molecular properties,aiming to explain how regulons grow and shrink, as bacteria tune their regulation to increase adaptation. [less ▲]

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