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Structural insights into the mechanism of GTP initiation of microtubule assembly

In eukaryotes, the dynamic assembly of microtubules (MT) plays an important role in numerous cellular processes. The underlying mechanism of GTP triggering MT assembly is still unknown. Here, we present cryo-EM structures of tubulin heterodimer at their GTP- and GDP-bound states, intermediate assemb...

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Autores principales: Zhou, Ju, Wang, Anhui, Song, Yinlong, Liu, Nan, Wang, Jia, Li, Yan, Liang, Xin, Li, Guohui, Chu, Huiying, Wang, Hong-Wei
Formato: Online Artículo Texto
Lenguaje:English
Publicado: Nature Publishing Group UK 2023
Materias:
Acceso en línea:https://www.ncbi.nlm.nih.gov/pmc/articles/PMC10519996/
https://www.ncbi.nlm.nih.gov/pubmed/37749104
http://dx.doi.org/10.1038/s41467-023-41615-w
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author Zhou, Ju
Wang, Anhui
Song, Yinlong
Liu, Nan
Wang, Jia
Li, Yan
Liang, Xin
Li, Guohui
Chu, Huiying
Wang, Hong-Wei
author_facet Zhou, Ju
Wang, Anhui
Song, Yinlong
Liu, Nan
Wang, Jia
Li, Yan
Liang, Xin
Li, Guohui
Chu, Huiying
Wang, Hong-Wei
author_sort Zhou, Ju
collection PubMed
description In eukaryotes, the dynamic assembly of microtubules (MT) plays an important role in numerous cellular processes. The underlying mechanism of GTP triggering MT assembly is still unknown. Here, we present cryo-EM structures of tubulin heterodimer at their GTP- and GDP-bound states, intermediate assembly states of GTP-tubulin, and final assembly stages of MT. Both GTP- and GDP-tubulin heterodimers adopt similar curved conformations with subtle flexibility differences. In head-to-tail oligomers of tubulin heterodimers, the inter-dimer interface of GDP-tubulin exhibits greater flexibility, particularly in tangential bending. Cryo-EM of the intermediate assembly states reveals two types of tubulin lateral contacts, “Tube-bond” and “MT-bond”. Further, molecular dynamics (MD) simulations show that GTP triggers lateral contact formation in MT assembly in multiple sequential steps, gradually straightening the curved tubulin heterodimers. Therefore, we propose a flexible model of GTP-initiated MT assembly, including the formation of longitudinal and lateral contacts, to explain the nucleation and assembly of MT.
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spelling pubmed-105199962023-09-27 Structural insights into the mechanism of GTP initiation of microtubule assembly Zhou, Ju Wang, Anhui Song, Yinlong Liu, Nan Wang, Jia Li, Yan Liang, Xin Li, Guohui Chu, Huiying Wang, Hong-Wei Nat Commun Article In eukaryotes, the dynamic assembly of microtubules (MT) plays an important role in numerous cellular processes. The underlying mechanism of GTP triggering MT assembly is still unknown. Here, we present cryo-EM structures of tubulin heterodimer at their GTP- and GDP-bound states, intermediate assembly states of GTP-tubulin, and final assembly stages of MT. Both GTP- and GDP-tubulin heterodimers adopt similar curved conformations with subtle flexibility differences. In head-to-tail oligomers of tubulin heterodimers, the inter-dimer interface of GDP-tubulin exhibits greater flexibility, particularly in tangential bending. Cryo-EM of the intermediate assembly states reveals two types of tubulin lateral contacts, “Tube-bond” and “MT-bond”. Further, molecular dynamics (MD) simulations show that GTP triggers lateral contact formation in MT assembly in multiple sequential steps, gradually straightening the curved tubulin heterodimers. Therefore, we propose a flexible model of GTP-initiated MT assembly, including the formation of longitudinal and lateral contacts, to explain the nucleation and assembly of MT. Nature Publishing Group UK 2023-09-25 /pmc/articles/PMC10519996/ /pubmed/37749104 http://dx.doi.org/10.1038/s41467-023-41615-w Text en © The Author(s) 2023 https://creativecommons.org/licenses/by/4.0/Open Access This article is licensed under a Creative Commons Attribution 4.0 International License, which permits use, sharing, adaptation, distribution and reproduction in any medium or format, as long as you give appropriate credit to the original author(s) and the source, provide a link to the Creative Commons licence, and indicate if changes were made. The images or other third party material in this article are included in the article’s Creative Commons licence, unless indicated otherwise in a credit line to the material. If material is not included in the article’s Creative Commons licence and your intended use is not permitted by statutory regulation or exceeds the permitted use, you will need to obtain permission directly from the copyright holder. To view a copy of this licence, visit http://creativecommons.org/licenses/by/4.0/ (https://creativecommons.org/licenses/by/4.0/) .
spellingShingle Article
Zhou, Ju
Wang, Anhui
Song, Yinlong
Liu, Nan
Wang, Jia
Li, Yan
Liang, Xin
Li, Guohui
Chu, Huiying
Wang, Hong-Wei
Structural insights into the mechanism of GTP initiation of microtubule assembly
title Structural insights into the mechanism of GTP initiation of microtubule assembly
title_full Structural insights into the mechanism of GTP initiation of microtubule assembly
title_fullStr Structural insights into the mechanism of GTP initiation of microtubule assembly
title_full_unstemmed Structural insights into the mechanism of GTP initiation of microtubule assembly
title_short Structural insights into the mechanism of GTP initiation of microtubule assembly
title_sort structural insights into the mechanism of gtp initiation of microtubule assembly
topic Article
url https://www.ncbi.nlm.nih.gov/pmc/articles/PMC10519996/
https://www.ncbi.nlm.nih.gov/pubmed/37749104
http://dx.doi.org/10.1038/s41467-023-41615-w
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