4fcv
From Proteopedia
Crystal structure of the C-terminal domain of ClpB
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 PubMedClpB is a ring-forming, ATP-dependent protein disaggregase that cooperates with the cognate Hsp70 system to recover functional protein from aggregates. How ClpB harnesses the energy of ATP binding and hydrolysis to facilitate the mechanical unfolding of previously aggregated, stress-damaged proteins remains unclear. Here, we present crystal structures of the ClpB D2 domain in the nucleotide-bound and -free states, and the fitted cryoEM structure of the D2 hexamer ring, which provide a structural understanding of the ATP power stroke that drives protein translocation through the ClpB hexamer. We demonstrate that the conformation of the substrate-translocating pore loop is coupled to the nucleotide state of the cis subunit, which is transmitted to the neighboring subunit via a conserved but structurally distinct intersubunit-signaling pathway common to diverse AAA+ machines. Furthermore, we found that an engineered, disulfide cross-linked ClpB hexamer is fully functional biochemically, suggesting that ClpB deoligomerization is not required for protein disaggregation. Structural basis for intersubunit signaling in a protein disaggregating machine.,Biter AB, Lee S, Sung N, Tsai FT Proc Natl Acad Sci U S A. 2012 Jul 31;109(31):12515-20. Epub 2012 Jul 16. PMID:22802670[2] From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine. See AlsoReferences
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