Substrate recognition by the AAA+ chaperone ClpB.
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.
Schlieker
Christian
C
Zentrum für Molekulare Biologie, Universität Heidelberg, Im Neuenheimer Feld 282, Heidelberg 69120, Germany.
Weibezahn
Jimena
J
Patzelt
Holger
H
Tessarz
Peter
P
Strub
Christine
C
Zeth
Kornelius
K
Erbse
Annette
A
Schneider-Mergener
Jens
J
Chin
Jason W
JW
Schultz
Peter G
PG
Bukau
Bernd
B
Mogk
Axel
A
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
D018832:Molecular Chaperones; D014443:Tyrosine; D000251:Adenosine Triphosphatases