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Structural insight into microtubule stabilization and kinesin inhibition by Tau family MAPs
The Tau family microtubule-associated proteins (MAPs) promote microtubule stabilization and regulate microtubule-based motility. They share the C-terminal microtubule-binding domain, which includes three to five tubulin-binding repeats. Different numbers of repeats formed by alternative splicing hav...
Autores principales: | , , , , , , , , , |
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Formato: | Online Artículo Texto |
Lenguaje: | English |
Publicado: |
Rockefeller University Press
2018
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Materias: | |
Acceso en línea: | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC6279373/ https://www.ncbi.nlm.nih.gov/pubmed/30275105 http://dx.doi.org/10.1083/jcb.201711182 |
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author | Shigematsu, Hideki Imasaki, Tsuyoshi Doki, Chihiro Sumi, Takuya Aoki, Mari Uchikubo-Kamo, Tomomi Sakamoto, Ayako Tokuraku, Kiyotaka Shirouzu, Mikako Nitta, Ryo |
author_facet | Shigematsu, Hideki Imasaki, Tsuyoshi Doki, Chihiro Sumi, Takuya Aoki, Mari Uchikubo-Kamo, Tomomi Sakamoto, Ayako Tokuraku, Kiyotaka Shirouzu, Mikako Nitta, Ryo |
author_sort | Shigematsu, Hideki |
collection | PubMed |
description | The Tau family microtubule-associated proteins (MAPs) promote microtubule stabilization and regulate microtubule-based motility. They share the C-terminal microtubule-binding domain, which includes three to five tubulin-binding repeats. Different numbers of repeats formed by alternative splicing have distinct effects on the activities of these proteins, and the distribution of these variants regulates fundamental physiological phenomena in cells. In this study, using cryo-EM, we visualized the MAP4 microtubule complex with the molecular motor kinesin-1. MAP4 bound to the C-terminal domains of tubulins along the protofilaments stabilizes the longitudinal contacts of the microtubule. The strongest bond of MAP4 was found around the intertubulin–dimer interface such that MAP4 coexists on the microtubule with kinesin-1 bound to the intratubulin–dimer interface as well. MAP4, consisting of five repeats, further folds and accumulates above the intertubulin–dimer interface, interfering with kinesin-1 movement. Therefore, these cryo-EM studies reveal new insight into the structural basis of microtubule stabilization and inhibition of kinesin motility by the Tau family MAPs. |
format | Online Article Text |
id | pubmed-6279373 |
institution | National Center for Biotechnology Information |
language | English |
publishDate | 2018 |
publisher | Rockefeller University Press |
record_format | MEDLINE/PubMed |
spelling | pubmed-62793732019-06-03 Structural insight into microtubule stabilization and kinesin inhibition by Tau family MAPs Shigematsu, Hideki Imasaki, Tsuyoshi Doki, Chihiro Sumi, Takuya Aoki, Mari Uchikubo-Kamo, Tomomi Sakamoto, Ayako Tokuraku, Kiyotaka Shirouzu, Mikako Nitta, Ryo J Cell Biol Research Articles The Tau family microtubule-associated proteins (MAPs) promote microtubule stabilization and regulate microtubule-based motility. They share the C-terminal microtubule-binding domain, which includes three to five tubulin-binding repeats. Different numbers of repeats formed by alternative splicing have distinct effects on the activities of these proteins, and the distribution of these variants regulates fundamental physiological phenomena in cells. In this study, using cryo-EM, we visualized the MAP4 microtubule complex with the molecular motor kinesin-1. MAP4 bound to the C-terminal domains of tubulins along the protofilaments stabilizes the longitudinal contacts of the microtubule. The strongest bond of MAP4 was found around the intertubulin–dimer interface such that MAP4 coexists on the microtubule with kinesin-1 bound to the intratubulin–dimer interface as well. MAP4, consisting of five repeats, further folds and accumulates above the intertubulin–dimer interface, interfering with kinesin-1 movement. Therefore, these cryo-EM studies reveal new insight into the structural basis of microtubule stabilization and inhibition of kinesin motility by the Tau family MAPs. Rockefeller University Press 2018-12-03 /pmc/articles/PMC6279373/ /pubmed/30275105 http://dx.doi.org/10.1083/jcb.201711182 Text en © 2018 Shigematsu et al. http://www.rupress.org/terms/https://creativecommons.org/licenses/by-nc-sa/4.0/This article is distributed under the terms of an Attribution–Noncommercial–Share Alike–No Mirror Sites license for the first six months after the publication date (see http://www.rupress.org/terms/). After six months it is available under a Creative Commons License (Attribution–Noncommercial–Share Alike 4.0 International license, as described at https://creativecommons.org/licenses/by-nc-sa/4.0/). |
spellingShingle | Research Articles Shigematsu, Hideki Imasaki, Tsuyoshi Doki, Chihiro Sumi, Takuya Aoki, Mari Uchikubo-Kamo, Tomomi Sakamoto, Ayako Tokuraku, Kiyotaka Shirouzu, Mikako Nitta, Ryo Structural insight into microtubule stabilization and kinesin inhibition by Tau family MAPs |
title | Structural insight into microtubule stabilization and kinesin inhibition by Tau family MAPs |
title_full | Structural insight into microtubule stabilization and kinesin inhibition by Tau family MAPs |
title_fullStr | Structural insight into microtubule stabilization and kinesin inhibition by Tau family MAPs |
title_full_unstemmed | Structural insight into microtubule stabilization and kinesin inhibition by Tau family MAPs |
title_short | Structural insight into microtubule stabilization and kinesin inhibition by Tau family MAPs |
title_sort | structural insight into microtubule stabilization and kinesin inhibition by tau family maps |
topic | Research Articles |
url | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC6279373/ https://www.ncbi.nlm.nih.gov/pubmed/30275105 http://dx.doi.org/10.1083/jcb.201711182 |
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