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Dev Cell. 2018 Oct 22;47(2):191-204.e8. doi: 10.1016/j.devcel.2018.08.023. Epub 2018 Sep 20.

The Structure and Dynamics of C. elegans Tubulin Reveals the Mechanistic Basis of Microtubule Growth.

Author information

1
Department of Biology, 1205 Avenue Docteur Penfield, Montréal, QC H3A 1B1, Canada.
2
Department of Computational Medicine and Bioinformatics, 100 Washtenaw Avenue, Ann Arbor, MI 48109, USA.
3
Experimental Center, Technische Universität Dresden, Faculty of Medicine, Fiedlerstraße 42, 01307 Dresden, Germany; Center for Membrane & Cell Physiology, University of Virginia and Department of Molecular Physiology & Biological Physics, 480 Ray C. Hung Drive, Charlottesville, VA 22903, USA.
4
Department of Biochemistry, 1959 NE Pacific Street, Seattle, WA 98195, USA.
5
Experimental Center, Technische Universität Dresden, Faculty of Medicine, Fiedlerstraße 42, 01307 Dresden, Germany.
6
Department of Biomedical Engineering, 2200 Bonisteel Boulevard, Ann Arbor, MI 48109, USA.
7
Department of Anatomy and Cell Biology, 3640 Rue University, Montréal, QC H3A 0C7, Canada.
8
Department of Biology, 1205 Avenue Docteur Penfield, Montréal, QC H3A 1B1, Canada. Electronic address: gary.brouhard@mcgill.ca.

Abstract

The dynamic instability of microtubules is a conserved and fundamental mechanism in eukaryotes. Yet microtubules from different species diverge in their growth rates, lattice structures, and responses to GTP hydrolysis. Therefore, we do not know what limits microtubule growth, what determines microtubule structure, or whether the mechanisms of dynamic instability are universal. Here, we studied microtubules from the nematode C. elegans, which have strikingly fast growth rates and non-canonical lattices in vivo. Using a reconstitution approach, we discovered that C. elegans microtubules combine intrinsically fast growth with very frequent catastrophes. We solved the structure of C. elegans microtubules to 4.8 Å and discovered sequence divergence in the lateral contact loops, one of which is ordered in C. elegans but unresolved in other species. We provide direct evidence that C. elegans tubulin has a higher free energy in solution and propose a model wherein the ordering of lateral contact loops activates tubulin for growth.

KEYWORDS:

C. elegans; catastrophe; cryo-EM; dynamic instability; microtubule; single molecule

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