Af. Neuwald et al., AAA(+): A class of chaperone-like ATPases associated with the assembly, operation, and disassembly of protein complexes, GENOME RES, 9(1), 1999, pp. 27-43
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.