Year: 2018
Type: article
Abstract: The ATP-dependent bacterial protein disaggregation machine, ClpB belonging to the AAA+ superfamily, refolds toxic protein aggregates into the native state in cooperation with the cognate Hsp70 partner. The ring-shaped hexamers of ClpB unfold and thread its protein substrate through the central pore. However, their function-related structural dynamics has remained elusive. Here we directly visualize ClpB using high-speed atomic force microscopy (HS-AFM) to gain a mechanistic insight into its disaggregation function. The HS-AFM movies demonstrate massive conformational changes of the hexameric ring during ATP hydrolysis, from a round ring to a spiral and even to a pair of twisted half-spirals. HS-AFM observations of Walker-motif mutants unveil crucial roles of ATP binding and hydrolysis in the oligomer formation and structural dynamics. Furthermore, repressed and hyperactive mutations result in significantly different oligomeric forms. These results provide a comprehensive view for the ATP-driven oligomeric-state transitions that enable ClpB to disentangle protein aggregates.
Source: Nature Communications
Institutions: Nagoya University, Konan University, Kanazawa University, The University of Osaka, National Institutes of Natural Sciences, The Exploratory Research Center on Life and Living Systems, National Institute for Physiological Sciences, The Graduate University for Advanced Studies, SOKENDAI, Institute for Molecular Science
Language: English
Topic: Heat shock proteins research
Subfield: Molecular Biology
Domain: Life Sciences
Open Access status: gold
Estimated APC paid: $6,990
Awards: Realization of nano-dynamics imaging of protein molecules in extremely soft membrane environments, Elucidation of energy conversion mechanism of a Na+-transporting rotary ATPase, G1668213617, G1794916765, G2020151399, G2166596079, G3158029195, G372004903, Engineering of a redox enzyme processively decomposing crystalline polysaccharide, G4453158857, G4644494512, G4702750479, G4782222130, G5183297446, G554711166, Development of variable-temperature high-speed AFM and its application to temperature-dependent ATPases, Physico-chemical and mathematical analyses of immune related signal induced by antibody aggregates, G5917072113, Opening up New Structural Biology by High-speed AFM, G6438406644, G6718509927, Disaggregation mechanism of a ring shaped AAA+ chaperon, G7838273862, G7879866177, G8525053510, G8853674104
OpenAlex ID: W2807478192