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Cryo-EM of dynein microtubule-binding domains shows how an axonemal dynein distorts the microtubule

Dyneins are motor proteins responsible for transport in the cytoplasm and the beating of axonemes in cilia and flagella. They bind and release microtubules via a compact microtubule-binding domain (MTBD) at the end of a coiled-coil stalk. We address how cytoplasmic and axonemal dynein MTBDs bind mic...

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Autores principales: Lacey, Samuel E, He, Shaoda, Scheres, Sjors HW, Carter, Andrew P
Formato: Online Artículo Texto
Lenguaje:English
Publicado: eLife Sciences Publications, Ltd 2019
Materias:
Acceso en línea:https://www.ncbi.nlm.nih.gov/pmc/articles/PMC6629372/
https://www.ncbi.nlm.nih.gov/pubmed/31264960
http://dx.doi.org/10.7554/eLife.47145
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author Lacey, Samuel E
He, Shaoda
Scheres, Sjors HW
Carter, Andrew P
author_facet Lacey, Samuel E
He, Shaoda
Scheres, Sjors HW
Carter, Andrew P
author_sort Lacey, Samuel E
collection PubMed
description Dyneins are motor proteins responsible for transport in the cytoplasm and the beating of axonemes in cilia and flagella. They bind and release microtubules via a compact microtubule-binding domain (MTBD) at the end of a coiled-coil stalk. We address how cytoplasmic and axonemal dynein MTBDs bind microtubules at near atomic resolution. We decorated microtubules with MTBDs of cytoplasmic dynein-1 and axonemal dynein DNAH7 and determined their cryo-EM structures using helical Relion. The majority of the MTBD is rigid upon binding, with the transition to the high-affinity state controlled by the movement of a single helix at the MTBD interface. DNAH7 contains an 18-residue insertion, found in many axonemal dyneins, that contacts the adjacent protofilament. Unexpectedly, we observe that DNAH7, but not dynein-1, induces large distortions in the microtubule cross-sectional curvature. This raises the possibility that dynein coordination in axonemes is mediated via conformational changes in the microtubule.
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spelling pubmed-66293722019-07-17 Cryo-EM of dynein microtubule-binding domains shows how an axonemal dynein distorts the microtubule Lacey, Samuel E He, Shaoda Scheres, Sjors HW Carter, Andrew P eLife Structural Biology and Molecular Biophysics Dyneins are motor proteins responsible for transport in the cytoplasm and the beating of axonemes in cilia and flagella. They bind and release microtubules via a compact microtubule-binding domain (MTBD) at the end of a coiled-coil stalk. We address how cytoplasmic and axonemal dynein MTBDs bind microtubules at near atomic resolution. We decorated microtubules with MTBDs of cytoplasmic dynein-1 and axonemal dynein DNAH7 and determined their cryo-EM structures using helical Relion. The majority of the MTBD is rigid upon binding, with the transition to the high-affinity state controlled by the movement of a single helix at the MTBD interface. DNAH7 contains an 18-residue insertion, found in many axonemal dyneins, that contacts the adjacent protofilament. Unexpectedly, we observe that DNAH7, but not dynein-1, induces large distortions in the microtubule cross-sectional curvature. This raises the possibility that dynein coordination in axonemes is mediated via conformational changes in the microtubule. eLife Sciences Publications, Ltd 2019-07-02 /pmc/articles/PMC6629372/ /pubmed/31264960 http://dx.doi.org/10.7554/eLife.47145 Text en © 2019, Lacey et al http://creativecommons.org/licenses/by/4.0/ http://creativecommons.org/licenses/by/4.0/This article is distributed under the terms of the Creative Commons Attribution License (http://creativecommons.org/licenses/by/4.0/) , which permits unrestricted use and redistribution provided that the original author and source are credited.
spellingShingle Structural Biology and Molecular Biophysics
Lacey, Samuel E
He, Shaoda
Scheres, Sjors HW
Carter, Andrew P
Cryo-EM of dynein microtubule-binding domains shows how an axonemal dynein distorts the microtubule
title Cryo-EM of dynein microtubule-binding domains shows how an axonemal dynein distorts the microtubule
title_full Cryo-EM of dynein microtubule-binding domains shows how an axonemal dynein distorts the microtubule
title_fullStr Cryo-EM of dynein microtubule-binding domains shows how an axonemal dynein distorts the microtubule
title_full_unstemmed Cryo-EM of dynein microtubule-binding domains shows how an axonemal dynein distorts the microtubule
title_short Cryo-EM of dynein microtubule-binding domains shows how an axonemal dynein distorts the microtubule
title_sort cryo-em of dynein microtubule-binding domains shows how an axonemal dynein distorts the microtubule
topic Structural Biology and Molecular Biophysics
url https://www.ncbi.nlm.nih.gov/pmc/articles/PMC6629372/
https://www.ncbi.nlm.nih.gov/pubmed/31264960
http://dx.doi.org/10.7554/eLife.47145
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