Cargando…

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...

Descripción completa

Detalles Bibliográficos
Autores principales: Luo, Wangxi, Demidov, Vladimir, Shen, Qi, Girão, Hugo, Chakraborty, Manas, Maiorov, Aleksandr, Ataullakhanov, Fazly I., Lin, Chenxiang, Maiato, Helder, Grishchuk, Ekaterina L.
Formato: Online Artículo Texto
Lenguaje:English
Publicado: American Association for the Advancement of Science 2023
Materias:
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
_version_ 1784863717441142784
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
work_keys_str_mv AT luowangxi clasp2recognizestubulinsexposedatthemicrotubuleplusendinanucleotidestatesensitivemanner
AT demidovvladimir clasp2recognizestubulinsexposedatthemicrotubuleplusendinanucleotidestatesensitivemanner
AT shenqi clasp2recognizestubulinsexposedatthemicrotubuleplusendinanucleotidestatesensitivemanner
AT giraohugo clasp2recognizestubulinsexposedatthemicrotubuleplusendinanucleotidestatesensitivemanner
AT chakrabortymanas clasp2recognizestubulinsexposedatthemicrotubuleplusendinanucleotidestatesensitivemanner
AT maiorovaleksandr clasp2recognizestubulinsexposedatthemicrotubuleplusendinanucleotidestatesensitivemanner
AT ataullakhanovfazlyi clasp2recognizestubulinsexposedatthemicrotubuleplusendinanucleotidestatesensitivemanner
AT linchenxiang clasp2recognizestubulinsexposedatthemicrotubuleplusendinanucleotidestatesensitivemanner
AT maiatohelder clasp2recognizestubulinsexposedatthemicrotubuleplusendinanucleotidestatesensitivemanner
AT grishchukekaterinal clasp2recognizestubulinsexposedatthemicrotubuleplusendinanucleotidestatesensitivemanner