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Tight bending of the Ndc80 complex provides intrinsic regulation of its binding to microtubules

Regulation of the outer kinetochore complex Ndc80 is essential to ensure correct kinetochore-microtubule attachments during mitosis. Here, we present a novel mechanism of regulation that is intrinsic to its structure; tight bending of the Ndc80 complex inhibits its microtubule binding. Using single...

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Detalles Bibliográficos
Autores principales: Scarborough, Emily Anne, Davis, Trisha N, Asbury, Charles L
Formato: Online Artículo Texto
Lenguaje:English
Publicado: eLife Sciences Publications, Ltd 2019
Materias:
Acceso en línea:https://www.ncbi.nlm.nih.gov/pmc/articles/PMC6516834/
https://www.ncbi.nlm.nih.gov/pubmed/31045495
http://dx.doi.org/10.7554/eLife.44489
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author Scarborough, Emily Anne
Davis, Trisha N
Asbury, Charles L
author_facet Scarborough, Emily Anne
Davis, Trisha N
Asbury, Charles L
author_sort Scarborough, Emily Anne
collection PubMed
description Regulation of the outer kinetochore complex Ndc80 is essential to ensure correct kinetochore-microtubule attachments during mitosis. Here, we present a novel mechanism of regulation that is intrinsic to its structure; tight bending of the Ndc80 complex inhibits its microtubule binding. Using single molecule Förster resonance energy transfer (FRET), we show that the Saccharomyces cerevisiae Ndc80 complex can fluctuate between straight and bent forms, and that binding of the complex to microtubules selects for straightened forms. The loop region of the complex enables its bent conformation, as deletion of the loop promotes straightening. In addition, the kinetochore complex MIND enhances microtubule binding by opposing the tightly bent, auto-inhibited conformation of the Ndc80 complex. We suggest that prior to its assembly at the kinetochore, the Ndc80 complex interchanges between bent (auto-inhibited) and open conformations. Once assembled, its association with MIND stabilizes the Ndc80 complex in a straightened form for higher affinity microtubule binding.
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spelling pubmed-65168342019-05-16 Tight bending of the Ndc80 complex provides intrinsic regulation of its binding to microtubules Scarborough, Emily Anne Davis, Trisha N Asbury, Charles L eLife Biochemistry and Chemical Biology Regulation of the outer kinetochore complex Ndc80 is essential to ensure correct kinetochore-microtubule attachments during mitosis. Here, we present a novel mechanism of regulation that is intrinsic to its structure; tight bending of the Ndc80 complex inhibits its microtubule binding. Using single molecule Förster resonance energy transfer (FRET), we show that the Saccharomyces cerevisiae Ndc80 complex can fluctuate between straight and bent forms, and that binding of the complex to microtubules selects for straightened forms. The loop region of the complex enables its bent conformation, as deletion of the loop promotes straightening. In addition, the kinetochore complex MIND enhances microtubule binding by opposing the tightly bent, auto-inhibited conformation of the Ndc80 complex. We suggest that prior to its assembly at the kinetochore, the Ndc80 complex interchanges between bent (auto-inhibited) and open conformations. Once assembled, its association with MIND stabilizes the Ndc80 complex in a straightened form for higher affinity microtubule binding. eLife Sciences Publications, Ltd 2019-05-02 /pmc/articles/PMC6516834/ /pubmed/31045495 http://dx.doi.org/10.7554/eLife.44489 Text en © 2019, Scarborough 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 Biochemistry and Chemical Biology
Scarborough, Emily Anne
Davis, Trisha N
Asbury, Charles L
Tight bending of the Ndc80 complex provides intrinsic regulation of its binding to microtubules
title Tight bending of the Ndc80 complex provides intrinsic regulation of its binding to microtubules
title_full Tight bending of the Ndc80 complex provides intrinsic regulation of its binding to microtubules
title_fullStr Tight bending of the Ndc80 complex provides intrinsic regulation of its binding to microtubules
title_full_unstemmed Tight bending of the Ndc80 complex provides intrinsic regulation of its binding to microtubules
title_short Tight bending of the Ndc80 complex provides intrinsic regulation of its binding to microtubules
title_sort tight bending of the ndc80 complex provides intrinsic regulation of its binding to microtubules
topic Biochemistry and Chemical Biology
url https://www.ncbi.nlm.nih.gov/pmc/articles/PMC6516834/
https://www.ncbi.nlm.nih.gov/pubmed/31045495
http://dx.doi.org/10.7554/eLife.44489
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