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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...

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Autores principales: van Breugel, Mark, Wilcken, Rainer, McLaughlin, Stephen H, Rutherford, Trevor J, Johnson, Christopher M
Formato: Online Artículo Texto
Lenguaje:English
Publicado: eLife Sciences Publications, Ltd 2014
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
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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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