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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...
Autores principales: | , , |
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Formato: | Online Artículo Texto |
Lenguaje: | English |
Publicado: |
eLife Sciences Publications, Ltd
2019
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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. |
format | Online Article Text |
id | pubmed-6516834 |
institution | National Center for Biotechnology Information |
language | English |
publishDate | 2019 |
publisher | eLife Sciences Publications, Ltd |
record_format | MEDLINE/PubMed |
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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