2011
DOI: 10.1126/science.1199325
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Structures of SAS-6 Suggest Its Organization in Centrioles

Abstract: Centrioles are cylindrical, ninefold symmetrical structures with peripheral triplet microtubules strictly required to template cilia and flagella. The highly conserved protein SAS-6 constitutes the center of the cartwheel assembly that scaffolds centrioles early in their biogenesis. We determined the x-ray structure of the amino-terminal domain of SAS-6 from zebrafish, and we show that recombinant SAS-6 self-associates in vitro into assemblies that resemble cartwheel centers. Point mutations are consistent wit… Show more

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Cited by 287 publications
(393 citation statements)
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“…Because visualization of cartwheels by electron microscopy has proven difficult in human cells, the number of stacks is unknown. Considering that each stacked hub is predicted to comprise 18 molecules (nine dimers) of Sas‐6 (van Breugel et al , 2011; Kitagawa et al , 2011), our prediction of 276 molecules of Sas‐6 per cartwheel‐containing centriole theoretically allows for the assembly of 15–16 stacks. This likely represents an upper limit, because not all Sas‐6 and STIL proteins are necessarily assembled into cartwheels at all times (Fong et al , 2014; Keller et al , 2014) and we also recognize that the number of stacks may differ between cell types.…”
Section: Discussionmentioning
confidence: 92%
“…Because visualization of cartwheels by electron microscopy has proven difficult in human cells, the number of stacks is unknown. Considering that each stacked hub is predicted to comprise 18 molecules (nine dimers) of Sas‐6 (van Breugel et al , 2011; Kitagawa et al , 2011), our prediction of 276 molecules of Sas‐6 per cartwheel‐containing centriole theoretically allows for the assembly of 15–16 stacks. This likely represents an upper limit, because not all Sas‐6 and STIL proteins are necessarily assembled into cartwheels at all times (Fong et al , 2014; Keller et al , 2014) and we also recognize that the number of stacks may differ between cell types.…”
Section: Discussionmentioning
confidence: 92%
“…An Ana2 tetramer may spatially arrange its conserved C-terminal STAN motifs to interact with Sas-6 and promote the Sas-6 oligomerization that underlies centriole cartwheel formation. Our SEC-MALS analysis of the Ana2M-LC8 complex reveals a stable, single-species complex consisting of four Ana2M molecules and eight LC8 molecules (Ana2M 4 -LC8 8 ). This stable complex was purified over two successive sizing columns, demonstrating its ready formation, and yielded a similar experimental mass in two independent purifications and SEC-MALS assays.…”
Section: Discussionmentioning
confidence: 99%
“…X-ray crystallography studies showed that SAS-6 comprises a globular N-terminal domain followed by a long coiled coil ( Figure 1) and a C-terminal disordered region. SAS-6 strongly dimerises in vitro and in vivo via its coiled-coil domain, and protein dimers further interact via their N-terminal domains to form oligomers with 9-fold radial symmetry on average [28][29][30][31]. The SAS-6 N-terminal domain bears strong structural resemblance to similar domains of XRCC4 and XLF (Figure 2), proteins involved in DNA repair and non-homologous end joining.…”
Section: Introductionmentioning
confidence: 99%
“…Further, similar to SAS-6, XRCC4 forms dimers via a coiled-coil domain, and it hetero-oligomerises with XLF via the globular N-terminal domains to form a spiral [32][33][34][35][36]. Most SAS-6 oligomers resolved to date are highly reminiscent of cartwheel rings, with a central hub derived from the N-terminal globular domains and the SAS-6 coiled coils comprising the cartwheel spokes [28,29,31]. Furthermore, disruption of SAS-6 oligomerisation abrogates formation of the central centriole scaffold and strongly hinders organelle assembly [29,31].…”
Section: Introductionmentioning
confidence: 99%
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