Allosteric coupling between the lid and interdomain linker in DnaK revealed by inhibitor binding studies

Markus Liebscher, Anna Roujeinikova

    Research output: Contribution to journalArticlepeer-review

    Abstract

    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. Copyright © 2009, American Society for Microbiology. All Rights Reserved.
    Original languageEnglish
    Pages (from-to)1456-1462
    Number of pages6
    JournalJournal of Bacteriology
    Volume191
    Issue number5
    DOIs
    Publication statusPublished - Mar 2009

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