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Review
. 2016 May 8;428(9 Pt B):1861-9.
doi: 10.1016/j.jmb.2015.11.015. Epub 2015 Dec 1.

Origin and Functional Evolution of the Cdc48/p97/VCP AAA+ Protein Unfolding and Remodeling Machine

Dominik Barthelme  1 , Robert T Sauer  2
Affiliations
Review

Origin and Functional Evolution of the Cdc48/p97/VCP AAA+ Protein Unfolding and Remodeling Machine

Dominik Barthelme et al. J Mol Biol. .

Abstract

The AAA+ Cdc48 ATPase (alias p97 or VCP) is a key player in multiple ubiquitin-dependent cell signaling, degradation, and quality control pathways. Central to these broad biological functions is the ability of Cdc48 to interact with a large number of adaptor proteins and to remodel macromolecular proteins and their complexes. Different models have been proposed to explain how Cdc48 might couple ATP hydrolysis to forcible unfolding, dissociation, or remodeling of cellular clients. In this review, we provide an overview of possible mechanisms for substrate unfolding/remodeling by this conserved and essential AAA+ protein machine and their adaption and possible biological function throughout evolution.

Keywords: AAA+ machine; human disease; protein remodeling.

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Figures

Figure 1
Figure 1
Domain and three-dimensional structure of Cdc48. (A) Cartoon depiction of the domains of Cdc48. (B) Side view of the Cdc48 hexamer (pdb code 3CF1) shown in surface representation. (C) Top view of the Cdc48 hexamer shown in surface representation. (D) Bottom view of the Cdc48 hexamer shown in surface representation.
Figure 2
Figure 2
Schematic view of a eukaryotic cell and numerous pathways in which Cdc48 and its adaptors have been implicated.
Figure 3
Figure 3
As shown in this phylogenetic tree (created at http://www.phylogeny.fr), Cdc48 enzymes are found in all three domains of life. The bacterial enzymes are most distantly related.
See this image and copyright information in PMC

References

    1. Hanson PI, Whiteheart SW. AAA+ proteins: have engine, will work. Nat Rev Mol Cell Biol. 2005;6:519–29. - PubMed
    1. Erzberger JP, Berger JM. Evolutionary relationships and structural mechanisms of AAA+ proteins. Annu Rev Biophys Biomol Struct. 2006;35:93–114. - PubMed
    1. Ogura T, Wilkinson AJ. AAA+ superfamily ATPases: common structure--diverse function. Genes Cells. 2001;6:575–97. - PubMed
    1. Neuwald AF, Aravind L, Spouge JL, Koonin EV. AAA+: A class of chaperone-like ATPases associated with the assembly, operation, and disassembly of protein complexes. Genome Res. 1999;9:27–43. - PubMed
    1. Meyer H, Bug M, Bremer S. Emerging functions of the VCP/p97 AAA-ATPase in the ubiquitin system. Nat Cell Biol. 2012;14:117–23. - PubMed

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