@article {Nithiananatham197558, author = {Stanley Nithiananatham and Francis J. McNally and Jawdat Al-Bassam}, title = {Structural Basis for Katanin Self-Assembly}, elocation-id = {197558}, year = {2017}, doi = {10.1101/197558}, publisher = {Cold Spring Harbor Laboratory}, abstract = {The reorganization of microtubules in mitosis, meiosis and development requires the microtubule-severing activity of katanin. Katanin is composed of a AAA ATPase subunit and a regulatory subunit. Microtubule severing requires ATP hydrolysis by katanin{\textquoteright}s conserved AAA ATPase domains. Whereas other AAA ATPases form stable hexamers, we show that wild-type katanin only forms heterodimers and heterotetramers. Heterododecamers were only observed for an ATP hydrolysis deficient mutant in the presence of ATP, suggesting an auto-inhibition mechanism that prevents oligomerization. X-ray structures of katanin{\textquoteright}s AAA ATPase in monomeric nucleotide-free and pseudo-oligomeric ADP-bound states reveal conformational changes in AAA subdomains and N and C-terminal expansion segments that explain this auto-inhibition of assembly. These data lead to a model in which self-inhibited heterodimers bind to a microtubule, then transition into an assembly-competent conformation upon ATP binding. Microtubule-bound heterododecamers then promote tubulin extraction from the microtubule prior to oligomer dissociation.}, URL = {https://www.biorxiv.org/content/early/2017/10/03/197558}, eprint = {https://www.biorxiv.org/content/early/2017/10/03/197558.full.pdf}, journal = {bioRxiv} }