What are ATPases associated with diverse cellular activities (AAA+)?

AAA+ enzymes (ATPases associated with various cellular activities) are a heterogenous group of molecular motor proteins. They usually generate mechanical work from binding and decomposing ATP (adenosine triphosphate), the universal energy source in the cell. AAA+ proteins usually act as oligomers and are often found at the core of essential multi protein assemblies involved in re-organisation and recycling processes of proteins, membranes or DNA in the cell. Despite sharing a strongly conserved nucleotide binding domain (see Figure), each AAA+ protein exhibits unique functional specificity and substrate selectivity. It is believed that accessory domains and proteins facilitate fine tuning of the AAA+ motor activity and thus confer specificity. However, the nature of these interactions as well as their impact on the motor activity of the AAA+ domains remains to be established.

Our lab aims to obtain a structural view on the complex conformational dynamics of these fascinating molecular machines in action. In particular, we want to understand how allosteric interactions between AAA+ modules in the active oligomer regulate ATPase activity and how accessory factors influence complex activity. The ultimate goal is to integrate structural data obtained by cryo electron microscopy and X-ray crystallography with mutational analysis and biophysical experiments in order to tackle severe disorders and illnesses stemming from malfunctioning molecular machines. 


Wendler, P., S. Ciniawsky, M. Kock, S. Kube (2012). Structure and function of the AAA+ nucleotide binding pocket. Biochim Biophys Acta  1823(1):2-4.



Left: All AAA+ proteins share a highly conserved ATP binding domain of approx. 230 residues. They belong to the superfamily of P-loop ATPases and contain several conserved motifs including Walker A (light blue), Walker B (dark blue), Arginine Finger (green), Glutamate Switch (orange), Sensor 1 (pink) and Sensor 2 (red). Right: The active form of most AAA+ proteins is a hexamer.