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Design principles of a microtubule polymerase
Stu2/XMAP215 microtubule polymerases use multiple tubulin-binding TOG domains and a lattice-binding basic region to processively promote faster elongation. How the domain composition and organization of these proteins dictate polymerase activity, end localization, and processivity is unknown. We sho...
Autores principales: | , , , , |
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Formato: | Online Artículo Texto |
Lenguaje: | English |
Publicado: |
eLife Sciences Publications, Ltd
2018
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Materias: | |
Acceso en línea: | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC5999394/ https://www.ncbi.nlm.nih.gov/pubmed/29897335 http://dx.doi.org/10.7554/eLife.34574 |
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author | Geyer, Elisabeth A Miller, Matthew P Brautigam, Chad A Biggins, Sue Rice, Luke M |
author_facet | Geyer, Elisabeth A Miller, Matthew P Brautigam, Chad A Biggins, Sue Rice, Luke M |
author_sort | Geyer, Elisabeth A |
collection | PubMed |
description | Stu2/XMAP215 microtubule polymerases use multiple tubulin-binding TOG domains and a lattice-binding basic region to processively promote faster elongation. How the domain composition and organization of these proteins dictate polymerase activity, end localization, and processivity is unknown. We show that polymerase activity does not require different kinds of TOGs, nor are there strict requirements for how the TOGs are linked. We identify an unexpected antagonism between the tubulin-binding TOGs and the lattice-binding basic region: lattice binding by the basic region is weak when at least two TOGs engage tubulins, strong when TOGs are empty. End-localization of Stu2 requires unpolymerized tubulin, at least two TOGs, and polymerase competence. We propose a ‘ratcheting’ model for processivity: transfer of tubulin from TOGs to the lattice activates the basic region, retaining the polymerase at the end for subsequent rounds of tubulin binding and incorporation. These results clarify design principles of the polymerase. |
format | Online Article Text |
id | pubmed-5999394 |
institution | National Center for Biotechnology Information |
language | English |
publishDate | 2018 |
publisher | eLife Sciences Publications, Ltd |
record_format | MEDLINE/PubMed |
spelling | pubmed-59993942018-06-15 Design principles of a microtubule polymerase Geyer, Elisabeth A Miller, Matthew P Brautigam, Chad A Biggins, Sue Rice, Luke M eLife Cell Biology Stu2/XMAP215 microtubule polymerases use multiple tubulin-binding TOG domains and a lattice-binding basic region to processively promote faster elongation. How the domain composition and organization of these proteins dictate polymerase activity, end localization, and processivity is unknown. We show that polymerase activity does not require different kinds of TOGs, nor are there strict requirements for how the TOGs are linked. We identify an unexpected antagonism between the tubulin-binding TOGs and the lattice-binding basic region: lattice binding by the basic region is weak when at least two TOGs engage tubulins, strong when TOGs are empty. End-localization of Stu2 requires unpolymerized tubulin, at least two TOGs, and polymerase competence. We propose a ‘ratcheting’ model for processivity: transfer of tubulin from TOGs to the lattice activates the basic region, retaining the polymerase at the end for subsequent rounds of tubulin binding and incorporation. These results clarify design principles of the polymerase. eLife Sciences Publications, Ltd 2018-06-13 /pmc/articles/PMC5999394/ /pubmed/29897335 http://dx.doi.org/10.7554/eLife.34574 Text en © 2018, Geyer 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 | Cell Biology Geyer, Elisabeth A Miller, Matthew P Brautigam, Chad A Biggins, Sue Rice, Luke M Design principles of a microtubule polymerase |
title | Design principles of a microtubule polymerase |
title_full | Design principles of a microtubule polymerase |
title_fullStr | Design principles of a microtubule polymerase |
title_full_unstemmed | Design principles of a microtubule polymerase |
title_short | Design principles of a microtubule polymerase |
title_sort | design principles of a microtubule polymerase |
topic | Cell Biology |
url | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC5999394/ https://www.ncbi.nlm.nih.gov/pubmed/29897335 http://dx.doi.org/10.7554/eLife.34574 |
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