Structural basis for disassembly of katanin heterododecamers

Stanley Nithianantham, Francis J. McNally, Jawdat Al-Bassam

Research output: Contribution to journalArticle

5 Citations (Scopus)

Abstract

The reorganization of microtubules in mitosis, meiosis, and development requires the microtubule-severing activity of katanin. Katanin is a heterodimer composed of an ATPase associ-ated 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 forms only a 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 revealed conformational changes in the AAA subdomains that explained the structural basis for the instability of the katanin heterododecamer. We propose that the rapid dissociation of katanin AAA oligomers may lead to an autoinhibited state that prevents inappropriate microtubule severing or that cyclical disassembly into heterodimers may critically contribute to the microtubule-severing mechanism.

Original languageEnglish (US)
Pages (from-to)10590-10605
Number of pages16
JournalJournal of Biological Chemistry
Volume293
Issue number27
DOIs
StatePublished - Jan 1 2018

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Microtubules
Adenosine Triphosphatases
Adenosine Triphosphate
Oligomers
Meiosis
Mitosis
Dimers
Adenosine Diphosphate
katanin
Hydrolysis
Nucleotides
Monomers
X-Rays
X rays

ASJC Scopus subject areas

  • Biochemistry
  • Molecular Biology
  • Cell Biology

Cite this

Structural basis for disassembly of katanin heterododecamers. / Nithianantham, Stanley; McNally, Francis J.; Al-Bassam, Jawdat.

In: Journal of Biological Chemistry, Vol. 293, No. 27, 01.01.2018, p. 10590-10605.

Research output: Contribution to journalArticle

Nithianantham, S, McNally, FJ & Al-Bassam, J 2018, 'Structural basis for disassembly of katanin heterododecamers', Journal of Biological Chemistry, vol. 293, no. 27, pp. 10590-10605. https://doi.org/10.1074/jbc.RA117.001215
Nithianantham, Stanley ; McNally, Francis J. ; Al-Bassam, Jawdat. / Structural basis for disassembly of katanin heterododecamers. In: Journal of Biological Chemistry. 2018 ; Vol. 293, No. 27. pp. 10590-10605.
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