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

• Published in: Developmental cell Vol. 47; no. 2; pp. 191 - 204.e8
• Main Authors: Chaaban, Sami, Jariwala, Shashank, Hsu, Chieh-Ting, Redemann, Stefanie, Kollman, Justin M., Müller-Reichert, Thomas, Sept, David, Bui, Khanh Huy, Brouhard, Gary J.
• Format: Journal Article
• Language: English
• Published: United States Elsevier Inc 22.10.2018
• Subjects: Animals; C. elegans; Caenorhabditis elegans - metabolism; Caenorhabditis elegans Proteins - physiology; catastrophe; cryo-EM; dynamic instability; Guanosine Triphosphate; microtubule; Microtubules - metabolism; Microtubules - physiology; Microtubules - ultrastructure; Models, Molecular; single molecule; Structure-Activity Relationship; Tubulin - metabolism; Tubulin - physiology; microtubule; single molecule; C. elegans; cryo-EM; catastrophe; dynamic instability
• ISSN: 1534-5807; 1878-1551
• DOI: 10.1016/j.devcel.2018.08.023

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. •C. elegans microtubules reconstituted in vitro are fast growing and short lived•Lateral contact loops are ordered in the C. elegans free dimer and in the lattice•C. elegans tubulin has a higher free energy in solution than B. taurus tubulin•Structuring of lateral contacts is a limiting step in tubulin activation and microtubule growth Microtubule polymerization involves complex structural transitions that are not fully understood. Chaaban et al. study microtubules from the nematode C. elegans, which have unique structures and dynamics in cells. They uncover a key limiting step in microtubule polymerization that involves the structuring of tubulin-tubulin interacting residues.