ATPase, AAA-type, core <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 functional variety seen between AAA ATPases is in part due to their extensive number of accessory domains and factors, and to their variable organisation within oligomeric assemblies, in addition to changes in key functional residues within the ATPase domain itself.</p><p>More information about these proteins can be found at Protein of the Month: AAA ATPases [<cite idref="PUB00033938"/>].</p>