Microtubule-severing enzymes (MSE's) are a class of ATPases within the AAA+ protein superfamily that facilitate severing of microtubules in the cell. Microtubules (MTs) are long filamentous proteins consisting of α- and β-tubulin dimer repeats found in various cellular structures like spindle fibers, cilia and flagella, and the cytoskeleton. Microtubule-severing enzymes are biological nanomachines that regulate the competing processes of microtubule proliferation and depolymerization, dynamic processes that are especially important in mitosis and meiosis and that heavily rely on the microtubule-severing enzyme katanin. In the cell katanin oligomerizes in the presence of ATP and binds to the carboxy terminal tail (CTT) of β-tubulin and possibly to the α-CTT as well; upon ATP hydrolysis the molecular motor removes the tubulin dimer from the microtubule lattice. The mechanism behind katanin binding and microtubule-severing, however, is under contention, and it is the purpose of this study to use molecular dynamics and normal mode analysis to identify a correct mechanism.

Investigating the catalytic mechanism of microtubule-severing enzymes

Macromolecular Chemistry: The Second Century

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ACS Spring 2020 National Meeting & Expo

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