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Assessing heterogeneity in oligomeric AAA+ machines

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Abstract

ATPases Associated with various cellular Activities (AAA+ ATPases) are molecular motors that use the energy of ATP binding and hydrolysis to remodel their target macromolecules. The majority of these ATPases form ring-shaped hexamers in which the active sites are located at the interfaces between neighboring subunits. Structural changes initiate in an active site and propagate to distant motor parts that interface and reshape the target macromolecules, thereby performing mechanical work. During the functioning cycle, the AAA+ motor transits through multiple distinct states. Ring architecture and placement of the catalytic sites at the intersubunit interfaces allow for a unique level of coordination among subunits of the motor. This in turn results in conformational differences among subunits and overall asymmetry of the motor ring as it functions. To date, a large amount of structural information has been gathered for different AAA+ motors, but even for the most characterized of them only a few structural states are known and the full mechanistic cycle cannot be yet reconstructed. Therefore, 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 oligomeric ensembles and heterogeneity within the ensembles. The second part of this review will concentrate on methods that assess structural and functional heterogeneity among subunits of AAA+ motors, thus bringing us closer to understanding the mechanism of these fascinating molecular motors.

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Acknowledgments

I would like to thank Drs. Marina Besprozvannaya, Lia Cardarelli, Baoyu Chen, Prashanti Iyer, Ryan Tsoi, and my anonymous reviewers for their helpful comments and suggestions on the manuscript. I apologize for not including a significant number of relevant and detailed studies from my colleagues in the field on account of limited space.

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  1. Department of Biomedical Engineering, Duke University, Durham, NC, 27708, USA

    Tatyana A. Sysoeva

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Sysoeva, T.A. Assessing heterogeneity in oligomeric AAA+ machines. Cell. Mol. Life Sci. 74, 1001–1018 (2017). https://doi.org/10.1007/s00018-016-2374-z

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