4lj5
ClpB NBD2 from T. thermophilus in complex with ADP
Structural highlights
FunctionCLPB_THET8 Part of a stress-induced multi-chaperone system, it is involved in the recovery of the cell from heat-induced damage, in cooperation with DnaK, DnaJ and GrpE. Acts before DnaK, in the processing of protein aggregates. Protein binding stimulates the ATPase activity; ATP hydrolysis unfolds the denatured protein aggregates, which probably helps expose new hydrophobic binding sites on the surface of ClpB-bound aggregates, contributing to the solubilization and refolding of denatured protein aggregates by DnaK.[1] Publication Abstract from PubMedATPases of the AAA+ superfamily are large oligomeric molecular machines that remodel their substrates by converting the energy from ATP hydrolysis into mechanical force. This study focuses on the molecular chaperone ClpB, the bacterial homologue of Hsp104, which reactivates aggregated proteins under cellular stress conditions. Based on high-resolution crystal structures in different nucleotide states, mutational analysis and nucleotide-binding kinetics experiments, the ATPase cycle of the C-terminal nucleotide-binding domain (NBD2), one of the motor subunits of this AAA+ disaggregation machine, is dissected mechanistically. The results provide insights into nucleotide sensing, explaining how the conserved sensor 2 motif contributes to the discrimination between ADP and ATP binding. Furthermore, the role of a conserved active-site arginine (Arg621), which controls binding of the essential Mg2+ ion, is described. Finally, a hypothesis is presented as to how the ATPase activity is regulated by a conformational switch that involves the essential Walker A lysine. In the proposed model, an unusual side-chain conformation of this highly conserved residue stabilizes a catalytically inactive state, thereby avoiding unnecessary ATP hydrolysis. Elements in nucleotide sensing and hydrolysis of the AAA+ disaggregation machine ClpB: a structure-based mechanistic dissection of a molecular motor.,Zeymer C, Barends TR, Werbeck ND, Schlichting I, Reinstein J Acta Crystallogr D Biol Crystallogr. 2014 Feb;70(Pt 2):582-95. doi:, 10.1107/S1399004713030629. Epub 2014 Jan 31. PMID:24531492[2] From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine. See AlsoReferences
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