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Multisite phosphorylation of the NDC80 complex gradually tunes its microtubule-binding affinity
Microtubule (MT) attachment to kinetochores is vitally important for cell division, but how these interactions are controlled by phosphorylation is not well known. We used quantitative approaches in vitro combined with molecular dynamics simulations to examine phosphoregulation of the NDC80 complex,...
Autores principales: | , , , , , |
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Formato: | Online Artículo Texto |
Lenguaje: | English |
Publicado: |
The American Society for Cell Biology
2015
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Materias: | |
Acceso en línea: | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC4436829/ https://www.ncbi.nlm.nih.gov/pubmed/25808492 http://dx.doi.org/10.1091/mbc.E14-11-1539 |
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author | Zaytsev, Anatoly V. Mick, Jeanne E. Maslennikov, Evgeny Nikashin, Boris DeLuca, Jennifer G. Grishchuk, Ekaterina L. |
author_facet | Zaytsev, Anatoly V. Mick, Jeanne E. Maslennikov, Evgeny Nikashin, Boris DeLuca, Jennifer G. Grishchuk, Ekaterina L. |
author_sort | Zaytsev, Anatoly V. |
collection | PubMed |
description | Microtubule (MT) attachment to kinetochores is vitally important for cell division, but how these interactions are controlled by phosphorylation is not well known. We used quantitative approaches in vitro combined with molecular dynamics simulations to examine phosphoregulation of the NDC80 complex, a core kinetochore component. We show that the outputs from multiple phosphorylation events on the unstructured tail of its Hec1 subunit are additively integrated to elicit gradual tuning of NDC80-MT binding both in vitro and in silico. Conformational plasticity of the Hec1 tail enables it to serve as a phosphorylation-controlled rheostat, providing a new paradigm for regulating the affinity of MT binders. We also show that cooperativity of NDC80 interactions is weak and is unaffected by NDC80 phosphorylation. This in vitro finding strongly supports our model that independent molecular binding events to MTs by individual NDC80 complexes, rather than their structured oligomers, regulate the dynamics and stability of kinetochore-MT attachments in dividing cells. |
format | Online Article Text |
id | pubmed-4436829 |
institution | National Center for Biotechnology Information |
language | English |
publishDate | 2015 |
publisher | The American Society for Cell Biology |
record_format | MEDLINE/PubMed |
spelling | pubmed-44368292015-07-30 Multisite phosphorylation of the NDC80 complex gradually tunes its microtubule-binding affinity Zaytsev, Anatoly V. Mick, Jeanne E. Maslennikov, Evgeny Nikashin, Boris DeLuca, Jennifer G. Grishchuk, Ekaterina L. Mol Biol Cell Articles Microtubule (MT) attachment to kinetochores is vitally important for cell division, but how these interactions are controlled by phosphorylation is not well known. We used quantitative approaches in vitro combined with molecular dynamics simulations to examine phosphoregulation of the NDC80 complex, a core kinetochore component. We show that the outputs from multiple phosphorylation events on the unstructured tail of its Hec1 subunit are additively integrated to elicit gradual tuning of NDC80-MT binding both in vitro and in silico. Conformational plasticity of the Hec1 tail enables it to serve as a phosphorylation-controlled rheostat, providing a new paradigm for regulating the affinity of MT binders. We also show that cooperativity of NDC80 interactions is weak and is unaffected by NDC80 phosphorylation. This in vitro finding strongly supports our model that independent molecular binding events to MTs by individual NDC80 complexes, rather than their structured oligomers, regulate the dynamics and stability of kinetochore-MT attachments in dividing cells. The American Society for Cell Biology 2015-05-15 /pmc/articles/PMC4436829/ /pubmed/25808492 http://dx.doi.org/10.1091/mbc.E14-11-1539 Text en © 2015 Zaytsev et al. This article is distributed by The American Society for Cell Biology under license from the author(s). Two months after publication it is available to the public under an Attribution–Noncommercial–Share Alike 3.0 Unported Creative Commons License (http://creativecommons.org/licenses/by-nc-sa/3.0). “ASCB®,” “The American Society for Cell Biology®,” and “Molecular Biology of the Cell®” are registered trademarks of The American Society for Cell Biology. |
spellingShingle | Articles Zaytsev, Anatoly V. Mick, Jeanne E. Maslennikov, Evgeny Nikashin, Boris DeLuca, Jennifer G. Grishchuk, Ekaterina L. Multisite phosphorylation of the NDC80 complex gradually tunes its microtubule-binding affinity |
title | Multisite phosphorylation of the NDC80 complex gradually tunes its microtubule-binding affinity |
title_full | Multisite phosphorylation of the NDC80 complex gradually tunes its microtubule-binding affinity |
title_fullStr | Multisite phosphorylation of the NDC80 complex gradually tunes its microtubule-binding affinity |
title_full_unstemmed | Multisite phosphorylation of the NDC80 complex gradually tunes its microtubule-binding affinity |
title_short | Multisite phosphorylation of the NDC80 complex gradually tunes its microtubule-binding affinity |
title_sort | multisite phosphorylation of the ndc80 complex gradually tunes its microtubule-binding affinity |
topic | Articles |
url | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC4436829/ https://www.ncbi.nlm.nih.gov/pubmed/25808492 http://dx.doi.org/10.1091/mbc.E14-11-1539 |
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