van, BM, Wilcken, R, McLaughlin, SH, Rutherford, TJ and Johnson, CM (2014) Structure of the SAS-6 cartwheel hub from Leishmania major. eLife.

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 A. 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. van Breugel et al

Item Type:	Article
Additional Information:	NIBR author: Wilcken, R institute: NIBR contributor address: (van Breugel, Wilcken, McLaughlin, Rutherford, Johnson) Medical Research Council Laboratory of Molecular Biology, Cambridge, United Kingdom (Wilcken) Novartis Institutes for BioMedical Research, Basel, Switzerland
Date Deposited:	13 Oct 2015 13:12
Last Modified:	13 Oct 2015 13:12
URI:	https://oak.novartis.com/id/eprint/22597