Cargando…

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...

Descripción completa

Detalles Bibliográficos
Autores principales: Shigematsu, Hideki, Imasaki, Tsuyoshi, Doki, Chihiro, Sumi, Takuya, Aoki, Mari, Uchikubo-Kamo, Tomomi, Sakamoto, Ayako, Tokuraku, Kiyotaka, Shirouzu, Mikako, Nitta, Ryo
Formato: Online Artículo Texto
Lenguaje:English
Publicado: Rockefeller University Press 2018
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
_version_ 1783378492711239680
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
work_keys_str_mv AT shigematsuhideki structuralinsightintomicrotubulestabilizationandkinesininhibitionbytaufamilymaps
AT imasakitsuyoshi structuralinsightintomicrotubulestabilizationandkinesininhibitionbytaufamilymaps
AT dokichihiro structuralinsightintomicrotubulestabilizationandkinesininhibitionbytaufamilymaps
AT sumitakuya structuralinsightintomicrotubulestabilizationandkinesininhibitionbytaufamilymaps
AT aokimari structuralinsightintomicrotubulestabilizationandkinesininhibitionbytaufamilymaps
AT uchikubokamotomomi structuralinsightintomicrotubulestabilizationandkinesininhibitionbytaufamilymaps
AT sakamotoayako structuralinsightintomicrotubulestabilizationandkinesininhibitionbytaufamilymaps
AT tokurakukiyotaka structuralinsightintomicrotubulestabilizationandkinesininhibitionbytaufamilymaps
AT shirouzumikako structuralinsightintomicrotubulestabilizationandkinesininhibitionbytaufamilymaps
AT nittaryo structuralinsightintomicrotubulestabilizationandkinesininhibitionbytaufamilymaps