Abstract:

<p>The reorganization of microtubules in mitosis, meiosis and development requires the microtubule-severing activity of katanin.&nbsp; 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&#39;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. &nbsp;Katanin oligomers consistent with hexamers of heterodimers or heterododecamers were only observed for an ATP hydrolysis deficient mutant in the presence of ATP. &nbsp;X-ray structures of katanin&#39;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.&nbsp; 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>