<p>AAA ATPases (ATPases Associated with diverse cellular Activities) form a large protein family and play a number of roles in the cell including cell-cycle regulation, protein proteolysis and disaggregation, organelle biogenesis and intracellular transport. Some of them function as molecular chaperones, subunits of proteolytic complexes or independent proteases (FtsH, Lon). They also act as DNA helicases and transcription factors [<cite idref="PUB00043605"/>].</p> <p>AAA ATPases belong to the AAA+ superfamily of ringshaped P-loop NTPases, which act via the energy-dependent unfolding of macromolecules [<cite idref="PUB00014779"/>, <cite idref="PUB00043606"/>]. There are six major clades of AAA domains (proteasome subunits, metalloproteases, domains D1 and D2 of ATPases with two AAA domains, the MSP1/katanin/spastin group and BCS1 and it homologues), as well as a number of deeply branching minor clades [<cite idref="PUB00014779"/>].</p><p>They assemble into oligomeric assemblies (often hexamers) that form a ring-shaped structure with a central pore. These proteins produce a molecular motor that couples ATP binding and hydrolysis to changes in conformational states that act upon a target substrate, either translocating or remodelling it [<cite idref="PUB00033933"/>].</p><p>They are found in all living organisms and share the common feature of the presence of a highly conserved AAA domain called the AAA module. This domain is responsible for ATP binding and hydrolysis. It contains 200-250 residues, among them there are two classical motifs, Walker A (GX4GKT) and Walker B (HyDE) [<cite idref="PUB00043605"/>].</p><p>The VAT protein of the archaebacterium <taxon tax_id="2303">Thermoplasma acidophilum</taxon>, like all other members of the Cdc48/p97 family of AAA ATPases, has two ATPase domains and a 185-residue amino-terminal substrate-recognition domain, VAT-N. VAT shows activity in protein folding and unfolding and thus shares the common function of these ATPases in disassembly and/or degradation of protein complexes. </p><p>VAT-N is composed of two equally sized subdomains. The amino-terminal subdomain VAT-Nn forms a double-psi beta-barrel whose pseudo-twofold symmetry is mirrored by an internal sequence repeat of 42 residues. The carboxy-terminal subdomain VAT-Nc forms a novel six-stranded beta-clam fold [<cite idref="PUB00007420"/>]. Together, VAT-Nn and VAT-Nc form a kidney-shaped structure, in close agreement with results from electron microscopy. VAT-Nn is related to numerous proteins including prokaryotic transcription factors, metabolic enzymes, the protease cofactors UFD1 and PrlF, and aspartic proteinases. </p>