The speed of GTP hydrolysis determines GTP cap size and controls microtubule stability

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  • dc.contributor.author Roostalu, Johanna
  • dc.contributor.author Thomas, Claire
  • dc.contributor.author Cade, Nicholas Ian
  • dc.contributor.author Kunzelmann, Simone
  • dc.contributor.author Taylor, Ian A.
  • dc.contributor.author Surrey, Thomas
  • dc.date.accessioned 2020-03-19T10:08:06Z
  • dc.date.available 2020-03-19T10:08:06Z
  • dc.date.issued 2020
  • dc.description.abstract Microtubules are cytoskeletal polymers whose function depends on their property to switch between states of growth and shrinkage. Growing microtubules are thought to be stabilized by a GTP cap at their ends. The nature of this cap, however, is still poorly understood. End Binding proteins (EBs) recruit a diverse range of regulators of microtubule function to growing microtubule ends. Whether the EB binding region is identical to the GTP cap is unclear. Using mutated human tubulin with blocked GTP hydrolysis, we demonstrate that EBs bind with high affinity to the GTP conformation of microtubules. Slowing-down GTP hydrolysis leads to extended GTP caps. We find that cap length determines microtubule stability and that the microtubule conformation changes gradually in the cap as GTP is hydrolyzed. These results demonstrate the critical importance of the kinetics of GTP hydrolysis for microtubule stability and establish that the GTP cap coincides with the EB-binding region.
  • dc.description.sponsorship This work was supported by grants FC001163 (Cancer Research UK; Medical Research Center; Wellcome Trust), 100145/Z/12/Z (Wellcome Trust) and Advanced Grant 323042 (European Research Council). It is also supported by the Spanish Ministry of Economy and Competitiveness, the Centro de Excelencia Severo Ochoa and CERCA Programme/Generalitat de Catalunya
  • dc.format.mimetype application/pdf
  • dc.identifier.citation Roostalu J, Thomas C, Cade NI, Kunzelmann S, Taylor IA, Surrey T. The speed of GTP hydrolysis determines GTP cap size and controls microtubule stability. Elife. 2020 Feb 13; 9. pii: e51992. DOI: 10.7554/eLife.51992
  • dc.identifier.doi http://dx.doi.org/10.7554/eLife.51992
  • dc.identifier.issn 2050-084X
  • dc.identifier.uri http://hdl.handle.net/10230/43949
  • dc.language.iso eng
  • dc.publisher eLife
  • dc.relation.ispartof Elife. 2020 Feb 13; 9. pii: e51992
  • dc.relation.projectID info:eu-repo/grantAgreement/EC/FP7/323042
  • dc.rights © 2020 Johanna Roostalu et al. This article is distributed under the terms of the Creative Commons Attribution License, which permits unrestricted use and redistribution provided that the original author and source are credited
  • dc.rights.accessRights info:eu-repo/semantics/openAccess
  • dc.rights.uri http://creativecommons.org/licenses/by/4.0/
  • dc.subject.other Microtúbuls
  • dc.subject.other Estabilitat
  • dc.title The speed of GTP hydrolysis determines GTP cap size and controls microtubule stability
  • dc.type info:eu-repo/semantics/article
  • dc.type.version info:eu-repo/semantics/publishedVersion

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