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Crystal structure of E. coli ClpB
Structural highlights
FunctionCLPB_ECOLI 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] [2] [3] Publication Abstract from PubMedThe hexameric AAA+ chaperone ClpB reactivates aggregated proteins in cooperation with the Hsp70 system. Essential for disaggregation, the ClpB middle domain (MD) is a coiled-coil propeller that binds Hsp70. Although the ClpB subunit structure is known, positioning of the MD in the hexamer and its mechanism of action are unclear. We obtained electron microscopy (EM) structures of the BAP variant of ClpB that binds the protease ClpP, clearly revealing MD density on the surface of the ClpB ring. Mutant analysis and asymmetric reconstructions show that MDs adopt diverse positions in a single ClpB hexamer. Adjacent, horizontally oriented MDs form head-to-tail contacts and repress ClpB activity by preventing Hsp70 interaction. Tilting of the MD breaks this contact, allowing Hsp70 binding, and releasing the contact in adjacent subunits. Our data suggest a wavelike activation of ClpB subunits around the ring.DOI: https://dx.doi.org/10.7554/eLife.02481.001. Head-to-tail interactions of the coiled-coil domains regulate ClpB activity and cooperation with Hsp70 in protein disaggregation.,Carroni M, Kummer E, Oguchi Y, Wendler P, Clare DK, Sinning I, Kopp J, Mogk A, Bukau B, Saibil HR Elife. 2014 Apr 30;3:e02481. doi: 10.7554/eLife.02481. PMID:24843029[4] From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine. See AlsoReferences
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