AAA+ Proteases: ATP-Fueled Machines of Protein Destruction
Top Cited Papers
- 7 July 2011
- journal article
- review article
- Published by Annual Reviews in Annual Review of Biochemistry
- Vol. 80 (1), 587-612
- https://doi.org/10.1146/annurev-biochem-060408-172623
Abstract
AAA+ family proteolytic machines (ClpXP, ClpAP, ClpCP, HslUV, Lon, FtsH, PAN/20S, and the 26S proteasome) perform protein quality control and are used in regulatory circuits in all cells. These machines contain a compartmental protease, with active sites sequestered in an interior chamber, and a hexameric ring of AAA+ ATPases. Substrate proteins are tethered to the ring, either directly or via adaptor proteins. An unstructured region of the substrate is engaged in the axial pore of the AAA+ ring, and cycles of ATP binding/hydrolysis drive conformational changes that create pulses of pulling that denature the substrate and translocate the unfolded polypeptide through the pore and into the degradation chamber. Here, we review our current understanding of the molecular mechanisms of substrate recognition, adaptor function, and ATP-fueled unfolding and translocation. The unfolding activities of these and related AAA+ machines can also be used to disassemble or remodel macromolecular complexes and to resolubilize aggregates.Keywords
This publication has 100 references indexed in Scilit:
- Control of Substrate Gating and Translocation into ClpP by Channel Residues and ClpX BindingJournal of Molecular Biology, 2010
- Structures of Asymmetric ClpX Hexamers Reveal Nucleotide-Dependent Motions in a AAA+ Protein-Unfolding MachineCell, 2009
- Prokaryotic Ubiquitin-Like Protein Pup Is Intrinsically DisorderedJournal of Molecular Biology, 2009
- Polypeptide Translocation by the AAA+ ClpXP Protease MachineCell Chemical Biology, 2009
- The antibiotic ADEP reprogrammes ClpP, switching it from a regulated to an uncontrolled proteaseEMBO Molecular Medicine, 2009
- Asymmetric Nucleotide Transactions of the HslUV ProteaseJournal of Molecular Biology, 2008
- Unique Contacts Direct High-Priority Recognition of the Tetrameric Mu Transposase-DNA Complex by the AAA+ Unfoldase ClpXMolecular Cell, 2008
- Diverse Pore Loops of the AAA+ ClpX Machine Mediate Unassisted and Adaptor-Dependent Recognition of ssrA-Tagged SubstratesMolecular Cell, 2008
- Atypical AAA+ Subunit Packing Creates an Expanded Cavity for Disaggregation by the Protein-Remodeling Factor Hsp104Cell, 2007
- Distinct Static and Dynamic Interactions Control ATPase-Peptidase Communication in a AAA+ ProteaseMolecular Cell, 2007