AAA+ ATPases: Achieving Diversity of Function with Conserved Machinery

  title={AAA+ ATPases: Achieving Diversity of Function with Conserved Machinery},
  author={Susan Roehl White and Brett P Lauring},
AAA+ adenosine triphosphatases (ATPases) are molecular machines that perform a wide variety of cellular functions. For instance, they can act in vesicle transport, organelle assembly, membrane dynamics and protein unfolding. In most cases, the ATPase domains of these proteins assemble into active ring‐shaped hexamers. As AAA+ proteins have a common structure, a central issue is determining how they use conserved mechanistic principles to accomplish specific biological actions. Here, we review… 
Assessing heterogeneity in oligomeric AAA+ machines
  • T. Sysoeva
  • Biology, Chemistry
    Cellular and Molecular Life Sciences
  • 2016
The first part of this work will provide a broad overview of what arrangements of AAA+ subunits have been structurally observed focusing on diversity of ATPase oligomericEnsembles and heterogeneity within the ensembles.
The molecular principles governing the activity and functional diversity of AAA+ proteins
How substrate-bound structures of AAA+ proteins have expanded the understanding of ATP-driven protein remodelling is reviewed, leading to a better understanding of the mechanisms of engagement and processing of their diverse substrates.
Mechanism of protein unfolding and polypeptide translocation by the AAA+ protease ClpXP
Strong structural similarities to other ATP-dependent pro-teases, as well as other ring translocases, suggest that the operating principles I havediscerned and describe here may generalize to other biological molecular motors.
Design framework of the MuA remodeling signal that confers preferential complex disassembly by the AAA + unfoldase ClpX by Lorraine Ling
A framework is provided to understand the design of recognition signals that specify and target macromolecular complexes to unfolding chaperones and remodelers of the AAA+ superfamily.
ATPase and protease domain movements in the bacterial AAA+ protease FtsH are driven by thermal fluctuations
It is suggested that thermal energy, but not chemical energy, provides the major driving force for conformational switching, while ATP, through a state reequilibration, introduces directionality into this process.
Engineered AAA+ proteases reveal principles of proteolysis at the mitochondrial inner membrane
The human YME1L protease is a membrane-anchored AAA+ enzyme that controls proteostasis at the inner membrane and intermembrane space of mitochondria and is capable of processively unfolding substrate proteins with substantial thermodynamic stabilities.


AAA+ proteins: have engine, will work
The structural organization of AAA+ proteins, the conformational changes they undergo, the range of different reactions they catalyse, and the diseases associated with their dysfunction are reviewed.
Rebuilt AAA + motors reveal operating principles for ATP-fuelled machines
It is shown that diverse geometric arrangements can support the enzymatic unfolding of protein substrates and translocation of the denatured polypeptide into the ClpP peptidase for degradation by covalently linking active and inactive subunits of the ATPase ClpX to form hexamers.
Evolutionary history and higher order classification of AAA+ ATPases.
Substrate recognition by the AAA+ chaperone ClpB
This work has identified a substrate-binding site of ClpB that is located at the central pore of the first AAA domain that contributes to substrate binding and its crucial role was confirmed by mutational analysis and direct crosslinking to substrates.
Diverse functions with a common regulator: ubiquitin takes command of an AAA ATPase.
  • Y. Ye
  • Biology
    Journal of structural biology
  • 2006
Cooperative kinetics of both Hsp104 ATPase domains and interdomain communication revealed by AAA sensor‐1 mutants
Hsp104 exhibits allosteric communication between the two sites in addition to homotypic cooperativity at both NBD1 and NBD2, demonstrating the importance of ATP hydrolysis as distinct from ATP binding at each site for Hsp104 function.
M domains couple the ClpB threading motor with the DnaK chaperone activity.