Abstract
H-NS, a protein found in Gram-negative bacteria, is involved in structuring the bacterial chromosome and acts as a global regulator for the expression of a wide variety of genes. These functions are correlated with both its DNA-binding and oligomerization properties. We have identified the minimal dimerization domain of H-NS, a 46 amino acid–long N-terminal fragment, and determined its structure using heteronuclear NMR spectroscopy. The highly intertwined structure of the dimer, reminiscent of a handshake, defines a new structural fold, which may offer a possibility for discriminating prokaryotic from eukaryotic proteins in drug design. Using mutational analysis, we also show that this N-terminal domain actively contributes to DNA binding, conversely to the current paradigm. Together, our data allows us to propose a model for the action of full length H-NS.
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Acknowledgements
J.P. Simore is greatly acknowledged for his help with the 800 NMR spectrometer; H. Buc, for constant support and advice; and M. Buckle, for numerous invaluable suggestions and critical reading of this manuscript. This work was supported by a grant from the Programme de Recherche en Biologie Fondamentale en Microbiologie et Maladies infectieuses, a doctoral fellowship grant (V.B.) from the MNERT and a EEC-TMR grant (M.K.).
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Bloch, V., Yang, Y., Margeat, E. et al. The H-NS dimerization domain defines a new fold contributing to DNA recognition. Nat Struct Mol Biol 10, 212–218 (2003). https://doi.org/10.1038/nsb904
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DOI: https://doi.org/10.1038/nsb904
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