Molecular dynamics study of Katanin oligomeres: A MT-severing enzyme

Microtubule (MT) severing enzymes, such as katanin, belong to the AAA ATPases family and play an important role in meiosis and mitosis through their cutting action on MTs. The severing action is driven by ATP hydrolysis, which induces transitions between distinct conformations of the oligomeric state of the severing enzyme. Two of these oligomeric structures, one in a spiral and the other in a closed ring arrangement, have recently been solved using cryo-EM. ATP is present in all the chains from the spiral conformation, while there is only partial occupancy of ATP in the ring conformation. At the same time, reports from the literature suggest that such high-order oligomeric states of severing enzymes are stable only in the presence of nucleotides and the substrate. We will describe our all-atom molecular dynamics simulations performed on the apo, the ATP bound, and minimal substrate-bound states of katanin. Our results help identify the factors that account for the stability of the oligomeric states and characterize the allosteric transitions that underlie the action of severing enzymes.