6EW0

Cryo-EM structure of GDP-microtubule co-polymerised with doublecortin and supplemented with Taxol

Summary for 6EW0

• Entry DOI: 10.2210/pdb6ew0/pdb
• EMDB information: 3961 3962 3963 3964 3965
• Descriptor: Tubulin alpha-1B chain, Tubulin beta chain, GUANOSINE-5'-TRIPHOSPHATE, ... (6 entities in total)
• Functional Keywords: microtubule, gtpase, tubulin, taxol, structural protein
• Biological source: Sus scrofa (Pig); More
• Total number of polymer chains: 12
• Total formula weight: 611740.84

Authors

Manka, S.W. (deposition date: 2017-11-03, release date: 2018-07-04, Last modification date: 2024-05-15)

Primary citation

Manka, S.W.,Moores, C.A.
The role of tubulin-tubulin lattice contacts in the mechanism of microtubule dynamic instability.
Nat. Struct. Mol. Biol., 25:607-615, 2018

PubMed Abstract: Microtubules form from longitudinally and laterally assembling tubulin α-β dimers. The assembly induces strain in tubulin, resulting in cycles of microtubule catastrophe and regrowth. This 'dynamic instability' is governed by GTP hydrolysis that renders the microtubule lattice unstable, but it is unclear how. We used a human microtubule nucleating and stabilizing neuronal protein, doublecortin, and high-resolution cryo-EM to capture tubulin's elusive hydrolysis intermediate GDP•Pi state, alongside the prehydrolysis analog GMPCPP state and the posthydrolysis GDP state with and without an anticancer drug, Taxol. GTP hydrolysis to GDP•Pi followed by Pi release constitutes two distinct structural transitions, causing unevenly distributed compressions of tubulin dimers, thereby tightening longitudinal and loosening lateral interdimer contacts. We conclude that microtubule catastrophe is triggered because the lateral contacts can no longer counteract the strain energy stored in the lattice, while reinforcement of the longitudinal contacts may support generation of force.

PubMed: 29967541
DOI: 10.1038/s41594-018-0087-8

Experimental method

ELECTRON MICROSCOPY (3.8 Å)