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The H-NS dimerization domain defines a new fold contributing to DNA recognition

Nature Structural & Molecular Biology volume 10, pages 212–218 (2003)Cite this article

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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Figure 1: Oligomeric state of H-NS(1–46).
Figure 2: NMR structure of H-NS(1–46).
Figure 3: The handshake fold.
Figure 4: A conserved domain contributing to DNA-binding.

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Protein Data Bank

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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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Author notes

  1. Vanessa Bloch, Yinshan Yang and Sylvie Rimsky: Both authors contributed equally to this work.

Authors and Affiliations

  1. Centre de Biochimie Structurale, CNRS-UMR 5048, INSERM-U554, Université de Montpellier I, 29 rue de Navacelles, Montpellier, 34090, France

    Vanessa Bloch, Yinshan Yang, Emmanuel Margeat, Alain Chavanieu, Marie Thérèse Augé, Stefan Arold & Michel Kochoyan

  2. Service de Biophysique des Fonctions Membranaires, DBJC/CEA and URA, CNRS 2096, C.E. Saclay, Gif/Yvette, 91191, cedex, France

    Bruno Robert

  3. Enzymologie et Cinétique Structurale, UMR 8113, Ecole Normale Supérieure de Cachan/CNRS/ Université Paris XI, 61 Avenue du Président Wilson, Cachan, 94235, cedex, France

    Sylvie Rimsky

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  1. Vanessa Bloch
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Correspondence to Michel Kochoyan.

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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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