Abstract
The Integration host factor (IHF) is a heterodimeric, sequence-specific DNA-binding and DNA-bending protein found in many types of eubacteria. The sole function of IHF is to bring about a sharp curvature in the target DNA (up to ≥ 160°). Such a drastic change in DNA shape has been evolutionarily recruited for controlling a large number of functions that depend on the architecture of given genomic sites. These include the organization of the bacterial nucleoid and the transcriptional control of distinct promoters. The growing availability of bacterial genomes allows a comparative approach to survey the regulatory breadth of IHF in a wider context. In this Chapter, we use the sequence of the IHF protein of the soil bacterium Pseudomonas putida as a starting point to examine in detail the basis of the recognition of DNA sequences by this nucleoid-associated protein, in particular the correlation between sequence conservation and DNA interaction for each of the IHF chains. This is greatly facilitated by comparing the protein sequence and the DNA binding specificity of IHF with those of similar proteins HU and the transcription factor 1 (TF1) from bacteriophage SPO1 of Bacillus subtilis. Mapping of the fully conserved amino acids and the protein-specific sites for each chain of the corresponding tridimensional structures finely correlates with those sites involved in DNA interactions and maintaining the protein dimer structure. The sequence conservation profile of the DNA-binding regions of these proteins shows that chain B of IHF is more closely related to HU/TF1 than to chain A of IHF, suggesting a separate evolutionary origin. Furthermore, some features of the DNA recognition mechanism seem to be exclusive to IHF and cannot be fulfilled by HU or TF1 proteins. HU and TF1 can be embraced by DNA as IHF can by the action of residues conserved in the three proteins (thereby explaining why HU/TF1 and IHF can be partially replaced by each other). In contrast, only the interactions mediated by tree-determinants (i.e. those residues that are specific for each chain of IHF) can afford a high DNA recognition specificity. These analyses highlight the importance of DNA binding versus DNA bending specificities for expansion of the regulatory space of such nucleoid-associated proteins.
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The work made in Authors’ Laboratory was supported by research grants of the Ministry of Science and Innovation, by contracts of the 6th Framework Programme of the EU and by Funds of the Autonomous Community of Madrid.
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Muñoz, A., Valls, M., de Lorenzo, V. (2010). Extreme DNA Bending: Molecular Basis of the Regulatory Breadth of IHF. In: Dame, R.T., Dorman, C.J. (eds) Bacterial Chromatin. Springer, Dordrecht. https://doi.org/10.1007/978-90-481-3473-1_16
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DOI: https://doi.org/10.1007/978-90-481-3473-1_16
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