title: Structure of the SAS-6 cartwheel hub from Leishmania major.
abstract: 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.
authors.affiliation: Medical Research Council Laboratory of Molecular Biology, Cambridge, United Kingdom.
authors.forename: Mark
authors.initials: M
authors.lastname: van Breugel
authors.forename: Rainer
authors.initials: R
authors.lastname: Wilcken
authors.forename: Stephen H
authors.initials: SH
authors.lastname: McLaughlin
authors.forename: Trevor J
authors.initials: TJ
authors.lastname: Rutherford
authors.forename: Christopher M
authors.initials: CM
authors.lastname: Johnson
mesh_terms: D002502:Centrioles / Q000737:chemistry*; D018360:Crystallography, X-Ray; D018320:Leishmania major / Q000737:chemistry*; D008958:Models, Molecular; D055503:Protein Multimerization; D015800:Protozoan Proteins / Q000737:chemistry* / Q000378:metabolism*
chemical_list: D015800:Protozoan Proteins
keywords: Leishmania; SAS-6; basal body; centriole; centrosome; trypanosomatid