Structures of SAS-6 coiled coil hold implications for the polarity of the centriolar cartwheel.
Structures of SAS-6 coiled coil hold implications for the polarity of the centriolar cartwheel.
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DOI：
10.1016/j.str.2022.02.005
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发表时间：
2022-05-05
期刊：
影响因子：
5.7
通讯作者：
Vakonakis, Ioannis
中科院分区：
文献类型：
--
作者：
Kantsadi, Anastassia L.;Hatzopoulos, Georgios N.;Gonczy, Pierre;Vakonakis, Ioannis
中心粒是真核生物的细胞器，在动物细胞中，中心粒模板纤毛和鞭毛的形成，以及组织微管网络和有丝分裂纺锤体。中心粒具有近端和远端极性，并由同样对称的中心支架（侧轮）赋予9倍径向对称。纺锤体组装异常蛋白6 （SAS-6）自组装成9倍径向对称的环状低聚物，这些低聚物通过一种未知的机制堆叠形成车轮。在这里，我们发现了由SAS-6的卷曲结构域介导的同质寡聚化相互作用。莱茵衣藻SAS-6盘状盘状复合物的晶体结构表明这种相互作用是不对称的，从而赋予车轮极性。利用冷冻电镜（cryo-EM）重构分析，我们证明氨基酸取代破坏这种不对称关联也会损害SAS-6环的堆叠。我们的工作提出了一种可能性，即SAS-6线圈固有的不对称相互作用为车轮组装提供了一个极性元素，这可能有助于向心近端-远端轴的建立。CrSAS-6螺旋结构域在溶液中形成高阶低聚物，晶体呈现对称和不对称构型。不对称的CrSAS-6螺旋结构对堆积形成侧轮具有重要意义。不对称的CrSAS-6螺旋结构可以为侧轮组装提供极性。向心蛋白SAS-6自组装成9倍径向对称的环，堆叠形成侧轮，这可能赋予中心粒对称性和手性。Kantsadi等人发现了由SAS-6的卷曲结构域介导的不对称同质寡聚化相互作用，这可能有助于建立中心粒的近端-远端极性
Centrioles are eukaryotic organelles that template the formation of cilia and flagella, as well as organize the microtubule network and the mitotic spindle in animal cells. Centrioles have proximal-distal polarity and a 9-fold radial symmetry imparted by a likewise symmetrical central scaffold, the cartwheel. The spindle assembly abnormal protein 6 (SAS-6) self-assembles into 9-fold radially symmetric ring-shaped oligomers that stack via an unknown mechanism to form the cartwheel. Here, we uncover a homo-oligomerization interaction mediated by the coiled-coil domain of SAS-6. Crystallographic structures of Chlamydomonas reinhardtii SAS-6 coiled-coil complexes suggest this interaction is asymmetric, thereby imparting polarity to the cartwheel. Using a cryoelectron microscopy (cryo-EM) reconstitution assay, we demonstrate that amino acid substitutions disrupting this asymmetric association also impair SAS-6 ring stacking. Our work raises the possibility that the asymmetric interaction inherent to SAS-6 coiled-coil provides a polar element for cartwheel assembly, which may assist the establishment of the centriolar proximal-distal axis. CrSAS-6 coiled-coil domain forms higher-order oligomers in solution and crystals CrSAS-6 coiled-coil complexes exhibit symmetric and asymmetric configurations Asymmetric CrSAS-6 coiled-coil complex is important for stacking to form cartwheel Asymmetric CrSAS-6 coiled-coil could provide polarity to cartwheel assembly The centriolar protein SAS-6 self-assembles into 9-fold radially symmetric rings that stack to form the cartwheel, which might impart symmetry and chirality to the centriole. Kantsadi et al. uncover an asymmetric homo-oligomerization interaction mediated by the coiled-coil domain of SAS-6 that may help establishing the proximal-distal polarity of the centriole
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DOI：
10.4161/worm.25214
发表时间：
2013-07-01
期刊：
Worm
影响因子：
--
作者：
Shimanovskaya E;Qiao R;Lesigang J;Dong G
通讯作者：
Dong G
DOI：
10.1098/rstb.2013.0458
发表时间：
2014-09-05
期刊：
Philosophical transactions of the Royal Society of London. Series B, Biological sciences
影响因子：
--
作者：
Hirono M
通讯作者：
Hirono M
影响因子：
11.4
作者：
Guichard, Paul;Chretien, Denis;Tassin, Anne-Marie
通讯作者：
Tassin, Anne-Marie
DOI：
10.1107/s090744490903947x
发表时间：
2010-04
期刊：
Acta crystallographica. Section D, Biological crystallography
影响因子：
--
作者：
Cowtan K
通讯作者：
Cowtan K
影响因子：
9.2
作者：
Azimzadeh, Juliette;Marshall, Wallace F.
通讯作者：
Marshall, Wallace F.