AAA+ ATPases
The AAA+ family of ATPases is an extension of the AAA (for ATPases associated
with a variety of cellular activities) family, originally defined to include
proteins with a common ~200 residue ATPase core that are involved in a variety
of functions, such as protein degradation (chaperones associated with proteosomes)
or vesicular fusion (the N-ethylmaleimide-sensitive fusion protein, NSF) (May
et al., 2001; Neuwald et al., 1999). The extended AAA+ family includes the clamp
loader subunits, such as gamma, as well replication proteins such as the MCMs
and cdc6 (Liu et al., 2000; May et al., 2001; Neuwald et al., 1999). The first
structures for members of the AAA+ family were determined for delta-prime (Guenther
et al., 1997) and for the D2 domain of NSF (Lenzen et al., 1998; Yu et al.,
1998). Subsequently, the structures of several other AAA+ ATPases have been
determined (for a recent review see (May et al., 2001)).
The relationship between Delta-Prime and AAA+ proteins was first discovered
on the basis of sequence comparisons by Andy Neuwald (Cold Spring Harbor Lab).
The picture below compares the first two domains of Delta-prime, on the left,
with that of NSF (on the right). The structure of NSF was determined simultaneously
by Axel Brunger and Bill Weis.
The structure of the hexameric assembly formed by one of the domains of the
AAA+ ATPase p97 is shown below.
References:
Guenther, B. D., Onrust, R., Sali, A., O'Donnell, M., and Kuriyan, J. (1997).
Crystal structure of the d' subunit of the clamp-loader complex of E. coli DNA
polymerase III. Cell 91, 335-345.
Lenzen, C. U., Steinmann, D., Whiteheart, S. W., and Weis, W. I. (1998). Crystal
structure of the hexamerization domain of N-ethylmaleimide- sensitive fusion
protein. Cell 94, 525-536.
Liu, J., Smith, C. L., DeRyckere, D., DeAngelis, K., Martin, G. S., and Berger,
J. M. (2000). Structure and function of Cdc6/Cdc18: implications for origin
recognition and checkpoint control. Mol Cell 6, 637-648.
May, A. P., Whiteheart, S. W., and Weis, W. I. (2001). Unraveling the Mechanism
of the Vesicle Transport ATPase NSF, the N- Ethylmaleimide-sensitive Factor.
J Biol Chem 276, 21991-21994.
Neuwald, A. F., Aravind, L., Spouge, J. L., and Koonin, E. V. (1999). AAA+:
A class of chaperone-like ATPases associated with the assembly, operation, and
disassembly of protein complexes. Genome Res 9, 27-43.
Yu, R. C., Hanson, P. I., Jahn, R., and Brunger, A. T. (1998). Structure of
the ATP-dependent oligomerization domain of N- ethylmaleimide sensitive factor
complexed with ATP. Nat Struct Biol 5, 803-811.