Structural Basis for Disassembly of Katanin Heterododecamers.
Publication Type:Journal Article
Source:J Biol Chem (2018)
<p>The reorganization of microtubules in mitosis, meiosis and development requires the microtubule-severing activity of katanin. Katanin is a heterodimer composed of an ATPase Associated with diverse cellular Activities (AAA) subunit and a regulatory subunit. Microtubule severing requires ATP hydrolysis by katanin's conserved AAA ATPase domains. Whereas other AAA ATPases form stable hexamers, we show that katanin only forms monomer or dimers of heterodimers in solution. Katanin oligomers consistent with hexamers of heterodimers or heterododecamers were only observed for an ATP hydrolysis deficient mutant in the presence of ATP. X-ray structures of katanin's AAA ATPase in monomeric nucleotide-free and pseudo-oligomeric ADP-bound states reveal conformational changes in AAA subdomains that explained the structural basis for instability of katanin heterododecamer. We propose that the rapid dissociation of katanin AAA oligomers may lead to an auto-inhibited state that prevents inappropriate microtubule severing, or that cyclical disassembly into heterodimers may critically contribute to the microtubule-severing mechanism.</p>