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CLASP2 recognizes tubulins exposed at the microtubule plus-end in a nucleotide state–sensitive manner
CLASPs (cytoplasmic linker-associated proteins) are ubiquitous stabilizers of microtubule dynamics, but their molecular targets at the microtubule plus-end are not understood. Using DNA origami–based reconstructions, we show that clusters of human CLASP2 form a load-bearing bond with terminal non-GT...
Autores principales: | , , , , , , , , , |
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Formato: | Online Artículo Texto |
Lenguaje: | English |
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American Association for the Advancement of Science
2023
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Acceso en línea: | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC9812398/ https://www.ncbi.nlm.nih.gov/pubmed/36598991 http://dx.doi.org/10.1126/sciadv.abq5404 |
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author | Luo, Wangxi Demidov, Vladimir Shen, Qi Girão, Hugo Chakraborty, Manas Maiorov, Aleksandr Ataullakhanov, Fazly I. Lin, Chenxiang Maiato, Helder Grishchuk, Ekaterina L. |
author_facet | Luo, Wangxi Demidov, Vladimir Shen, Qi Girão, Hugo Chakraborty, Manas Maiorov, Aleksandr Ataullakhanov, Fazly I. Lin, Chenxiang Maiato, Helder Grishchuk, Ekaterina L. |
author_sort | Luo, Wangxi |
collection | PubMed |
description | CLASPs (cytoplasmic linker-associated proteins) are ubiquitous stabilizers of microtubule dynamics, but their molecular targets at the microtubule plus-end are not understood. Using DNA origami–based reconstructions, we show that clusters of human CLASP2 form a load-bearing bond with terminal non-GTP tubulins at the stabilized microtubule tip. This activity relies on the unconventional TOG2 domain of CLASP2, which releases its high-affinity bond with non-GTP dimers upon their conversion into polymerization-competent GTP-tubulins. The ability of CLASP2 to recognize nucleotide-specific tubulin conformation and stabilize the catastrophe-promoting non-GTP tubulins intertwines with the previously underappreciated exchange between GDP and GTP at terminal tubulins. We propose that TOG2-dependent stabilization of sporadically occurring non-GTP tubulins represents a distinct molecular mechanism to suppress catastrophe at the freely assembling microtubule ends and to promote persistent tubulin assembly at the load-bearing tethered ends, such as at the kinetochores in dividing cells. |
format | Online Article Text |
id | pubmed-9812398 |
institution | National Center for Biotechnology Information |
language | English |
publishDate | 2023 |
publisher | American Association for the Advancement of Science |
record_format | MEDLINE/PubMed |
spelling | pubmed-98123982023-01-10 CLASP2 recognizes tubulins exposed at the microtubule plus-end in a nucleotide state–sensitive manner Luo, Wangxi Demidov, Vladimir Shen, Qi Girão, Hugo Chakraborty, Manas Maiorov, Aleksandr Ataullakhanov, Fazly I. Lin, Chenxiang Maiato, Helder Grishchuk, Ekaterina L. Sci Adv Biomedicine and Life Sciences CLASPs (cytoplasmic linker-associated proteins) are ubiquitous stabilizers of microtubule dynamics, but their molecular targets at the microtubule plus-end are not understood. Using DNA origami–based reconstructions, we show that clusters of human CLASP2 form a load-bearing bond with terminal non-GTP tubulins at the stabilized microtubule tip. This activity relies on the unconventional TOG2 domain of CLASP2, which releases its high-affinity bond with non-GTP dimers upon their conversion into polymerization-competent GTP-tubulins. The ability of CLASP2 to recognize nucleotide-specific tubulin conformation and stabilize the catastrophe-promoting non-GTP tubulins intertwines with the previously underappreciated exchange between GDP and GTP at terminal tubulins. We propose that TOG2-dependent stabilization of sporadically occurring non-GTP tubulins represents a distinct molecular mechanism to suppress catastrophe at the freely assembling microtubule ends and to promote persistent tubulin assembly at the load-bearing tethered ends, such as at the kinetochores in dividing cells. American Association for the Advancement of Science 2023-01-04 /pmc/articles/PMC9812398/ /pubmed/36598991 http://dx.doi.org/10.1126/sciadv.abq5404 Text en Copyright © 2023 The Authors, some rights reserved; exclusive licensee American Association for the Advancement of Science. No claim to original U.S. Government Works. Distributed under a Creative Commons Attribution NonCommercial License 4.0 (CC BY-NC). https://creativecommons.org/licenses/by-nc/4.0/This is an open-access article distributed under the terms of the Creative Commons Attribution-NonCommercial license (https://creativecommons.org/licenses/by-nc/4.0/) , which permits use, distribution, and reproduction in any medium, so long as the resultant use is not for commercial advantage and provided the original work is properly cited. |
spellingShingle | Biomedicine and Life Sciences Luo, Wangxi Demidov, Vladimir Shen, Qi Girão, Hugo Chakraborty, Manas Maiorov, Aleksandr Ataullakhanov, Fazly I. Lin, Chenxiang Maiato, Helder Grishchuk, Ekaterina L. CLASP2 recognizes tubulins exposed at the microtubule plus-end in a nucleotide state–sensitive manner |
title | CLASP2 recognizes tubulins exposed at the microtubule plus-end in a nucleotide state–sensitive manner |
title_full | CLASP2 recognizes tubulins exposed at the microtubule plus-end in a nucleotide state–sensitive manner |
title_fullStr | CLASP2 recognizes tubulins exposed at the microtubule plus-end in a nucleotide state–sensitive manner |
title_full_unstemmed | CLASP2 recognizes tubulins exposed at the microtubule plus-end in a nucleotide state–sensitive manner |
title_short | CLASP2 recognizes tubulins exposed at the microtubule plus-end in a nucleotide state–sensitive manner |
title_sort | clasp2 recognizes tubulins exposed at the microtubule plus-end in a nucleotide state–sensitive manner |
topic | Biomedicine and Life Sciences |
url | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC9812398/ https://www.ncbi.nlm.nih.gov/pubmed/36598991 http://dx.doi.org/10.1126/sciadv.abq5404 |
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