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Template-free 13-protofilament microtubule–MAP assembly visualized at 8 Å resolution
Microtubule-associated proteins (MAPs) are essential for regulating and organizing cellular microtubules (MTs). However, our mechanistic understanding of MAP function is limited by a lack of detailed structural information. Using cryo-electron microscopy and single particle algorithms, we solved the...
Autores principales: | , , , , , , , , |
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Formato: | Texto |
Lenguaje: | English |
Publicado: |
The Rockefeller University Press
2010
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Materias: | |
Acceso en línea: | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC3003314/ https://www.ncbi.nlm.nih.gov/pubmed/20974813 http://dx.doi.org/10.1083/jcb.201007081 |
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author | Fourniol, Franck J. Sindelar, Charles V. Amigues, Béatrice Clare, Daniel K. Thomas, Geraint Perderiset, Mylène Francis, Fiona Houdusse, Anne Moores, Carolyn A. |
author_facet | Fourniol, Franck J. Sindelar, Charles V. Amigues, Béatrice Clare, Daniel K. Thomas, Geraint Perderiset, Mylène Francis, Fiona Houdusse, Anne Moores, Carolyn A. |
author_sort | Fourniol, Franck J. |
collection | PubMed |
description | Microtubule-associated proteins (MAPs) are essential for regulating and organizing cellular microtubules (MTs). However, our mechanistic understanding of MAP function is limited by a lack of detailed structural information. Using cryo-electron microscopy and single particle algorithms, we solved the 8 Å structure of doublecortin (DCX)-stabilized MTs. Because of DCX’s unusual ability to specifically nucleate and stabilize 13-protofilament MTs, our reconstruction provides unprecedented insight into the structure of MTs with an in vivo architecture, and in the absence of a stabilizing drug. DCX specifically recognizes the corner of four tubulin dimers, a binding mode ideally suited to stabilizing both lateral and longitudinal lattice contacts. A striking consequence of this is that DCX does not bind the MT seam. DCX binding on the MT surface indirectly stabilizes conserved tubulin–tubulin lateral contacts in the MT lumen, operating independently of the nucleotide bound to tubulin. DCX’s exquisite binding selectivity uncovers important insights into regulation of cellular MTs. |
format | Text |
id | pubmed-3003314 |
institution | National Center for Biotechnology Information |
language | English |
publishDate | 2010 |
publisher | The Rockefeller University Press |
record_format | MEDLINE/PubMed |
spelling | pubmed-30033142011-05-01 Template-free 13-protofilament microtubule–MAP assembly visualized at 8 Å resolution Fourniol, Franck J. Sindelar, Charles V. Amigues, Béatrice Clare, Daniel K. Thomas, Geraint Perderiset, Mylène Francis, Fiona Houdusse, Anne Moores, Carolyn A. J Cell Biol Research Articles Microtubule-associated proteins (MAPs) are essential for regulating and organizing cellular microtubules (MTs). However, our mechanistic understanding of MAP function is limited by a lack of detailed structural information. Using cryo-electron microscopy and single particle algorithms, we solved the 8 Å structure of doublecortin (DCX)-stabilized MTs. Because of DCX’s unusual ability to specifically nucleate and stabilize 13-protofilament MTs, our reconstruction provides unprecedented insight into the structure of MTs with an in vivo architecture, and in the absence of a stabilizing drug. DCX specifically recognizes the corner of four tubulin dimers, a binding mode ideally suited to stabilizing both lateral and longitudinal lattice contacts. A striking consequence of this is that DCX does not bind the MT seam. DCX binding on the MT surface indirectly stabilizes conserved tubulin–tubulin lateral contacts in the MT lumen, operating independently of the nucleotide bound to tubulin. DCX’s exquisite binding selectivity uncovers important insights into regulation of cellular MTs. The Rockefeller University Press 2010-11-01 /pmc/articles/PMC3003314/ /pubmed/20974813 http://dx.doi.org/10.1083/jcb.201007081 Text en © 2010 Fourniol et al. This article is distributed under the terms of an Attribution–Noncommercial–Share Alike–No Mirror Sites license for the first six months after the publication date (see http://www.rupress.org/terms). After six months it is available under a Creative Commons License (Attribution–Noncommercial–Share Alike 3.0 Unported license, as described at http://creativecommons.org/licenses/by-nc-sa/3.0/). |
spellingShingle | Research Articles Fourniol, Franck J. Sindelar, Charles V. Amigues, Béatrice Clare, Daniel K. Thomas, Geraint Perderiset, Mylène Francis, Fiona Houdusse, Anne Moores, Carolyn A. Template-free 13-protofilament microtubule–MAP assembly visualized at 8 Å resolution |
title | Template-free 13-protofilament microtubule–MAP assembly visualized at 8 Å resolution |
title_full | Template-free 13-protofilament microtubule–MAP assembly visualized at 8 Å resolution |
title_fullStr | Template-free 13-protofilament microtubule–MAP assembly visualized at 8 Å resolution |
title_full_unstemmed | Template-free 13-protofilament microtubule–MAP assembly visualized at 8 Å resolution |
title_short | Template-free 13-protofilament microtubule–MAP assembly visualized at 8 Å resolution |
title_sort | template-free 13-protofilament microtubule–map assembly visualized at 8 å resolution |
topic | Research Articles |
url | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC3003314/ https://www.ncbi.nlm.nih.gov/pubmed/20974813 http://dx.doi.org/10.1083/jcb.201007081 |
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