title: Allosteric coupling between the lid and interdomain linker in DnaK revealed by inhibitor binding studies.
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 beta-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.
authors.affiliation: Martin Luther University Halle-Wittenberg, Saale, Germany.
authors.forename: Markus
authors.initials: M
authors.lastname: Liebscher
authors.forename: Anna
authors.initials: A
authors.lastname: Roujeinikova
mesh_terms: D000495:Allosteric Site; D000595:Amino Acid Sequence; D000818:Animals; D023181:Antimicrobial Cationic Peptides / Q000737:chemistry / Q000378:metabolism* / Q000494:pharmacology; D001665:Binding Sites; D001667:Binding, Competitive; D018360:Crystallography, X-Ray; D004926:Escherichia coli / Q000378:metabolism*; D029968:Escherichia coli Proteins / Q000037:antagonists & inhibitors* / Q000737:chemistry* / Q000378:metabolism; D018840:HSP70 Heat-Shock Proteins / Q000037:antagonists & inhibitors* / Q000737:chemistry* / Q000378:metabolism; D019476:Insect Proteins / Q000737:chemistry / Q000378:metabolism* / Q000494:pharmacology; D008958:Models, Molecular; D018832:Molecular Chaperones / Q000037:antagonists & inhibitors / Q000737:chemistry* / Q000378:metabolism; D008969:Molecular Sequence Data
chemical_list: D023181:Antimicrobial Cationic Peptides; D029968:Escherichia coli Proteins; D018840:HSP70 Heat-Shock Proteins; D019476:Insect Proteins; D018832:Molecular Chaperones; C087710:pyrrhocoricin protein, Pyrrhocoris apterus; C063842:dnaK protein, E coli