Journal
PROCEEDINGS OF THE NATIONAL ACADEMY OF SCIENCES OF THE UNITED STATES OF AMERICA
Volume 109, Issue 30, Pages 12011-12016Publisher
NATL ACAD SCIENCES
DOI: 10.1073/pnas.1204129109
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Funding
- Centre National de la Recherche Scientifique
- Agence Nationale de Recherches [ANR-09-BLAN-0071]
- Fondation pour la Recherche Medicale [DEQ20081213979]
- Cancer Research United Kingdom
- European Community [227764]
- Agence Nationale de la Recherche (ANR) [ANR-09-BLAN-0071] Funding Source: Agence Nationale de la Recherche (ANR)
- Cancer Research UK [14256] Funding Source: researchfish
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Microtubules are cytoskeleton filaments consisting of alpha beta-tubulin heterodimers. They switch between phases of growth and shrinkage. The underlying mechanism of this property, called dynamic instability, is not fully understood. Here, we identified a designed ankyrin repeat protein (DARPin) that interferes with microtubule assembly in a unique manner. The X-ray structure of its complex with GTP-tubulin shows that it binds to the beta-tubulin surface exposed at microtubule (+) ends. The details of the structure provide insight into the role of GTP in microtubule polymerization and the conformational state of tubulin at the very microtubule end. They show in particular that GTP facilitates the tubulin structural switch that accompanies microtubule assembly but does not trigger it in unpolymerized tubulin. Total internal reflection fluorescence microscopy revealed that the DARPin specifically blocks growth at the microtubule (+) end by a selective end-capping mechanism, ultimately favoring microtubule disassembly from that end. DARPins promise to become designable tools for the dissection of microtubule dynamic properties selective for either of their two different ends.
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