Structural model for differential cap maturation at growing microtubule ends.

ELife
Juan Estévez-GallegoMaria A Oliva

Abstract

Microtubules (MTs) are hollow cylinders made of tubulin, a GTPase responsible for essential functions during cell growth and division, and thus, key target for anti-tumor drugs. In MTs, GTP hydrolysis triggers structural changes in the lattice, which are responsible for interaction with regulatory factors. The stabilizing GTP-cap is a hallmark of MTs and the mechanism of the chemical-structural link between the GTP hydrolysis site and the MT lattice is a matter of debate. We have analyzed the structure of tubulin and MTs assembled in the presence of fluoride salts that mimic the GTP-bound and GDP•Pi transition states. Our results challenge current models because tubulin does not change axial length upon GTP hydrolysis. Moreover, analysis of the structure of MTs assembled in the presence of several nucleotide analogues and of taxol allows us to propose that previously described lattice expansion could be a post-hydrolysis stage involved in Pi release.

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Citations

Sep 3, 2020·PLoS Computational Biology·Maxim Igaev, Helmut Grubmüller
Jul 9, 2020·Proceedings of the National Academy of Sciences of the United States of America·Garrett E DebsCharles V Sindelar
Feb 5, 2021·Annals of Biomedical Engineering·Mahya Hemmat, David J Odde
May 26, 2021·Current Biology : CB·Joseph M Cleary, William O Hancock
Aug 20, 2021·Nature Reviews. Molecular Cell Biology·Nikita B Gudimchuk, J Richard McIntosh

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Methods Mentioned

BETA
GTPase
GTP-cap
GTPases
X-ray
size exclusion chromatography
electron microscopy
PISA

Software Mentioned

PHENIX
Excel
AIMLESS
XRTools
Sigma
Plot
XDS
ImageJ
TubuleJ
PHASER

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