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Nat Rev Mol Cell Biol. 2019 Nov 21. doi: 10.1038/s41580-019-0183-6. [Epub ahead of print]

The molecular principles governing the activity and functional diversity of AAA+ proteins.

Author information

1
Department of Integrative Structural and Computational Biology, The Scripps Research Institute, La Jolla, CA, USA.
2
Department of Integrative Structural and Computational Biology, The Scripps Research Institute, La Jolla, CA, USA. glander@scripps.edu.

Abstract

ATPases associated with diverse cellular activities (AAA+ proteins) are macromolecular machines that convert the chemical energy contained in ATP molecules into powerful mechanical forces to remodel a vast array of cellular substrates, including protein aggregates, macromolecular complexes and polymers. AAA+ proteins have key functionalities encompassing unfolding and disassembly of such substrates in different subcellular localizations and, hence, power a plethora of fundamental cellular processes, including protein quality control, cytoskeleton remodelling and membrane dynamics. Over the past 35 years, many of the key elements required for AAA+ activity have been identified through genetic, biochemical and structural analyses. However, how ATP powers substrate remodelling and whether a shared mechanism underlies the functional diversity of the AAA+ superfamily were uncertain. Advances in cryo-electron microscopy have enabled high-resolution structure determination of AAA+ proteins trapped in the act of processing substrates, revealing a conserved core mechanism of action. It has also become apparent that this common mechanistic principle is structurally adjusted to carry out a diverse array of biological functions. Here, we review how substrate-bound structures of AAA+ proteins have expanded our understanding of ATP-driven protein remodelling.

PMID:
31754261
DOI:
10.1038/s41580-019-0183-6

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