title: Substrate recognition by the AAA+ chaperone ClpB.
abstract: The AAA+ protein ClpB cooperates with the DnaK chaperone system to solubilize and refold proteins from an aggregated state. The substrate-binding site of ClpB and the mechanism of ClpB-dependent protein disaggregation are largely unknown. Here we identified a substrate-binding site of ClpB that is located at the central pore of the first AAA domain. The conserved Tyr251 residue that lines the central pore contributes to substrate binding and its crucial role was confirmed by mutational analysis and direct crosslinking to substrates. Because the positioning of an aromatic residue at the central pore is conserved in many AAA+ proteins, a central substrate-binding site involving this residue may be a common feature of this protein family. The location of the identified binding site also suggests a possible translocation mechanism as an integral part of the ClpB-dependent disaggregation reaction.
authors.affiliation: Zentrum für Molekulare Biologie, Universität Heidelberg, Im Neuenheimer Feld 282, Heidelberg 69120, Germany.
authors.forename: Christian
authors.initials: C
authors.lastname: Schlieker
authors.forename: Jimena
authors.initials: J
authors.lastname: Weibezahn
authors.forename: Holger
authors.initials: H
authors.lastname: Patzelt
authors.forename: Peter
authors.initials: P
authors.lastname: Tessarz
authors.forename: Christine
authors.initials: C
authors.lastname: Strub
authors.forename: Kornelius
authors.initials: K
authors.lastname: Zeth
authors.forename: Annette
authors.initials: A
authors.lastname: Erbse
authors.forename: Jens
authors.initials: J
authors.lastname: Schneider-Mergener
authors.forename: Jason W
authors.initials: JW
authors.lastname: Chin
authors.forename: Peter G
authors.initials: PG
authors.lastname: Schultz
authors.forename: Bernd
authors.initials: B
authors.lastname: Bukau
authors.forename: Axel
authors.initials: A
authors.lastname: Mogk
mesh_terms: D000251:Adenosine Triphosphatases / Q000378:metabolism; D000595:Amino Acid Sequence; D001667:Binding, Competitive; D008956:Models, Chemical; D018832:Molecular Chaperones / Q000378:metabolism*; D008969:Molecular Sequence Data; D016296:Mutagenesis; D017386:Sequence Homology, Amino Acid; D013379:Substrate Specificity; D014443:Tyrosine / Q000378:metabolism
chemical_list: D018832:Molecular Chaperones; D014443:Tyrosine; D000251:Adenosine Triphosphatases