AAA(+): A class of chaperone-like ATPases associated with the assembly, operation, and disassembly of protein complexes

Using a combination of computer methods for iterative database searches and multiple sequence alignment, we show that protein sequences related to the AAA family of ATPases are far more prevalent than reported previously. Amo ng these are regulatory components of Lon and Clp proteases, proteins invol ved in DNA replication, recombination, and restriction (including subunits of the origin recognition complex, replication factor C proteins, MCM DNA-l icensing factors and the bacterial DnaA, RuvB, and McrB proteins) prokaryot ic NtrC-related transcription regulators, the Bacillus sporulation protein SpoVJ, M2+, and Co2+ Chelatases, the Halobacterium GvpN gas Vesicle synthes is protein, dynein motor proteins, TorsinA, and Rubisco activase. Alignment of these sequences, in light of the structures of the clamp loader delta' subunit of Escherichia coli DNA polymerase III and the hexamerization compo nent of N-ethylmaleimide-sensitive fusion protein, provides structural and mechanistic insights into these proteins, collectively designated the AAA() class. Whole-genome analysis indicates that this class is ancient and has undergone considerable functional divergence prior to the emergence of the major divisions of life. These proteins often perform chaperone-like funct ions that assist in the assembly, operation, or disassembly of protein comp lexes. The hexameric architecture often associated with this class can prov ide a hole through which DNA or RNA can be thread; this may be important fo r assembly or remodeling of DNA-protein complexes.