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Journal of Bacteriology, March 2009, p. 1456-1462, Vol. 191, No. 5
0021-9193/09/$08.00+0     doi:10.1128/JB.01131-08
Copyright © 2009, American Society for Microbiology. All Rights Reserved.

Allosteric Coupling between the Lid and Interdomain Linker in DnaK Revealed by Inhibitor Binding Studies{triangledown}

Markus Liebscher1 and Anna Roujeinikova2*

Biocenter, Martin Luther University Halle-Wittenberg, Weinbergweg 22, D-06120 Halle (Saale), Germany,1 Manchester Interdisciplinary Biocenter, Faculty of Life Sciences, University of Manchester, 131 Princess Street, Manchester M1 7DN, United Kingdom2

Received 12 August 2008/ Accepted 10 December 2008

The molecular chaperone DnaK assists protein folding and refolding, translocation across membranes, and regulation of the heat shock response. In Escherichia coli, the protein is a target for insect-derived antimicrobial peptides, pyrrhocoricins. We present here the X-ray crystallographic analysis of the E. coli DnaK substrate-binding domain in complex with pyrrhocoricin-derived peptide inhibitors. The structures show that pyrrhocoricins act as site-specific, dual-mode (competitive and allosteric) inhibitors, occupying the substrate-binding tunnel and disrupting the latch between the lid and the β-sandwich. Our structural analysis revealed an allosteric coupling between the movements of the lid and the interdomain linker, identifying a previously unknown mechanism of the lid-mediated regulation of the chaperone cycle.

* Corresponding author. Mailing address: Manchester Interdisciplinary Biocenter, Faculty of Life Sciences, University of Manchester, 131 Princess St., Manchester M1 7DN, United Kingdom. Phone: 44 161 3065155. Fax: 44 161 3065201. E-mail: Anna.Roujeinikova{at}manchester.ac.uk

{triangledown} Published ahead of print on 19 December 2008.

Journal of Bacteriology, March 2009, p. 1456-1462, Vol. 191, No. 5
0021-9193/09/$08.00+0     doi:10.1128/JB.01131-08
Copyright © 2009, American Society for Microbiology. All Rights Reserved.





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