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Structure of the SAS-6 cartwheel hub from Leishmania major
Centrioles are cylindrical cell organelles with a ninefold symmetric peripheral microtubule array that is essential to template cilia and flagella. They are built around a central cartwheel assembly that is organized through homo-oligomerization of the centriolar protein SAS-6, but whether SAS-6 sel...
Autores principales: | , , , , |
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Formato: | Online Artículo Texto |
Lenguaje: | English |
Publicado: |
eLife Sciences Publications, Ltd
2014
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Materias: | |
Acceso en línea: | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC3939493/ https://www.ncbi.nlm.nih.gov/pubmed/24596152 http://dx.doi.org/10.7554/eLife.01812 |
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author | van Breugel, Mark Wilcken, Rainer McLaughlin, Stephen H Rutherford, Trevor J Johnson, Christopher M |
author_facet | van Breugel, Mark Wilcken, Rainer McLaughlin, Stephen H Rutherford, Trevor J Johnson, Christopher M |
author_sort | van Breugel, Mark |
collection | PubMed |
description | Centrioles are cylindrical cell organelles with a ninefold symmetric peripheral microtubule array that is essential to template cilia and flagella. They are built around a central cartwheel assembly that is organized through homo-oligomerization of the centriolar protein SAS-6, but whether SAS-6 self-assembly can dictate cartwheel and thereby centriole symmetry is unclear. Here we show that Leishmania major SAS-6 crystallizes as a 9-fold symmetric cartwheel and provide the X-ray structure of this assembly at a resolution of 3.5 Å. We furthermore demonstrate that oligomerization of Leishmania SAS-6 can be inhibited by a small molecule in vitro and provide indications for its binding site. Our results firmly establish that SAS-6 can impose cartwheel symmetry on its own and indicate how this process might occur mechanistically in vivo. Importantly, our data also provide a proof-of-principle that inhibition of SAS-6 oligomerization by small molecules is feasible. DOI: http://dx.doi.org/10.7554/eLife.01812.001 |
format | Online Article Text |
id | pubmed-3939493 |
institution | National Center for Biotechnology Information |
language | English |
publishDate | 2014 |
publisher | eLife Sciences Publications, Ltd |
record_format | MEDLINE/PubMed |
spelling | pubmed-39394932014-03-06 Structure of the SAS-6 cartwheel hub from Leishmania major van Breugel, Mark Wilcken, Rainer McLaughlin, Stephen H Rutherford, Trevor J Johnson, Christopher M eLife Biochemistry Centrioles are cylindrical cell organelles with a ninefold symmetric peripheral microtubule array that is essential to template cilia and flagella. They are built around a central cartwheel assembly that is organized through homo-oligomerization of the centriolar protein SAS-6, but whether SAS-6 self-assembly can dictate cartwheel and thereby centriole symmetry is unclear. Here we show that Leishmania major SAS-6 crystallizes as a 9-fold symmetric cartwheel and provide the X-ray structure of this assembly at a resolution of 3.5 Å. We furthermore demonstrate that oligomerization of Leishmania SAS-6 can be inhibited by a small molecule in vitro and provide indications for its binding site. Our results firmly establish that SAS-6 can impose cartwheel symmetry on its own and indicate how this process might occur mechanistically in vivo. Importantly, our data also provide a proof-of-principle that inhibition of SAS-6 oligomerization by small molecules is feasible. DOI: http://dx.doi.org/10.7554/eLife.01812.001 eLife Sciences Publications, Ltd 2014-03-04 /pmc/articles/PMC3939493/ /pubmed/24596152 http://dx.doi.org/10.7554/eLife.01812 Text en Copyright © 2014, van Breugel et al http://creativecommons.org/licenses/by/3.0/ This article is distributed under the terms of the Creative Commons Attribution License (http://creativecommons.org/licenses/by/3.0/) , which permits unrestricted use and redistribution provided that the original author and source are credited. |
spellingShingle | Biochemistry van Breugel, Mark Wilcken, Rainer McLaughlin, Stephen H Rutherford, Trevor J Johnson, Christopher M Structure of the SAS-6 cartwheel hub from Leishmania major |
title | Structure of the SAS-6 cartwheel hub from Leishmania major |
title_full | Structure of the SAS-6 cartwheel hub from Leishmania major |
title_fullStr | Structure of the SAS-6 cartwheel hub from Leishmania major |
title_full_unstemmed | Structure of the SAS-6 cartwheel hub from Leishmania major |
title_short | Structure of the SAS-6 cartwheel hub from Leishmania major |
title_sort | structure of the sas-6 cartwheel hub from leishmania major |
topic | Biochemistry |
url | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC3939493/ https://www.ncbi.nlm.nih.gov/pubmed/24596152 http://dx.doi.org/10.7554/eLife.01812 |
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