AAA ATPases

AAA ATPases associated with a variety of cellular activities E(MFP)AB 87(122) 112(159) 1BMF... 

The six ATPases belong to the rather large family of AAA ATPases (for ATPases Associated with a variety of cellular Activities) whose eukaryotic members include the motor protein dynein, the membrane fusion factor NSF, and the chaperone... 

Frohlich, K U., Diamant, N., and Bar-Nun, S. AAA-ATPase p97/ Cdc48p, a cytosolic chaperone required for endoplasmic reticulum-assodated protein degradation. Mol Cell Biol 2002, 22, 626-34. 

ATP-dependent proteases are complex proteolytic machines. They are present in eubacteria, archaebacteria, in eukaryotic organelles and, as the 20S or 26S proteasome, in the eukaryotic cytosol and nucleoplasm. The activators of all known ATP-dependent proteases are related. They all contain an AAA(+) ATPase domain as a module (Neuwald et al. 1999) and are thought to assemble into hexameric particles or, in the case of 26S proteasomes, are present in six variants in the 19S activators (Glickman et al. 1999). Like the ATPases, the proteolytic components of the ATP-dependent proteases form higher order complexes, but unlike for the ATPases, the symmetry of the protease assemblies varies, and the folds of the subunits need not be related. ClpP is a serine protease, FtsH a metalloprotease, and HslV and the proteasomes from archaebacteria and eubacteria are threomne proteases. 

The component subunits of PA700 range in size from 112 to 28 kDa. The S nomenclature identifies subunits on the basis of their relative mobility during SDS polyacrylamide-gel electrophoresis, whereas the Rpt/Rpn nomenclature distinguishes between the AAA ATPase subunits (Regulatory particle triple-A protein) and the non-AAA ATPase subunits (Regulatory particle non-ATPase) (see below). 

AAA ATPases associated with different cellular activities... 

Sequencing of several archaeal genomes revealed the existence of genes with high sequence similarity to the ATPases of the eukaryotic 19S regulator. The deduced 50 kDa proteins have N-terminal coiled-coils, a hallmark of proteasomal AAA ATPases, and C-terminal AAA domains. The Methanococcus jannaschii protein was expressed in E. coli and purified as a 650 kD complex with nucleotidase activity. When mixed with proteasomes from Thermoplasma, degradation of substrate proteins was stimulated up to... 

Hashimoto T (2003) Plastid division its origins and evolution. Int Rev Cytol 222 63-98 Iyer LM, Leipe D, Koonin EV, Aravind L (2004) Evolutionary history and higher order classification of AAA+ ATPases. J Struct Biol 146 11-31 Javaux EJ, Knoll AH, Walter MR (2001) Morphological and ecological complexity in early eukaryotic ecosystems. Nature 412 66-69... 

Propose a structure. The 19S subunit of the proteasome contains 6 subunits that are members of the AAA ATPase family. Other members of this large family are associated into homohexamers with six-fold symmetry. Propose a structure for the AAA ATPases within the 19S proteasome. How might you test and refine your prediction ... 

Figure 34.9. Dynein Head-Domain Model. ATP is bound in the first of six P-loop NTPase domains (numbered) in this model for the head domain of dynein. The model is based on electron micrographs and the structures of other members of the AAA ATPase family. 

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