Structural analysis of the human SYCE2-TEX12 complex provides molecular insights into synaptonemal complex assembly.

Structural analysis of the human SYCE2-TEX12 complex provides molecular insights into synaptonemal complex assembly.
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DOI:
10.1098/rsob.120099
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发表时间:
2012-07
期刊:
影响因子:
5.8
通讯作者:
Pellegrini L
Pellegrini L
中科院分区:
生物学2区
文献类型:
--
作者:
Davies OR;Maman JD;Pellegrini L

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减数分裂的成功完成对所有有性生殖的生物体都是必不可少的。联会复合体(SC)是一个大的蛋白质结构,在减数分裂过程中将同源染色体连接在一起,为减数分裂重组和交换形成提供结构框架。SC形成的错误与不育、复发性流产和非整倍体有关。目前缺乏有关SC组装动态过程的分子信息,严重限制了我们对其在减数分裂中功能的理解。在这里,我们提供了第一个SC蛋白组分的生化和结构分析,并提出了其功能在SC组装的结构基础。我们发现,人类SC蛋白SYCE 2和TEX 12形成了一个高度稳定的,组成型复合物,并定义了负责其同型和异型相互作用的区域。生物物理分析表明,SYCE 2-TEX 12复合物是等摩尔的异八聚体,由SYCE 2四聚体和两个TEX 12二聚体缔合形成。电子显微镜显示,生化重组SYCE 2-TEX 12复合物自发组装成丝状结构,类似于SC中心元件(CE)的已知物理特征。我们的研究结果可以与现有的生物学数据相结合,在一个模型的染色体突触驱动的SYCE 2-TEX 12高阶结构内的CE的SC的增长。
The successful completion of meiosis is essential for all sexually reproducing organisms. The synaptonemal complex (SC) is a large proteinaceous structure that holds together homologous chromosomes during meiosis, providing the structural framework for meiotic recombination and crossover formation. Errors in SC formation are associated with infertility, recurrent miscarriage and aneuploidy. The current lack of molecular information about the dynamic process of SC assembly severely restricts our understanding of its function in meiosis. Here, we provide the first biochemical and structural analysis of an SC protein component and propose a structural basis for its function in SC assembly. We show that human SC proteins SYCE2 and TEX12 form a highly stable, constitutive complex, and define the regions responsible for their homotypic and heterotypic interactions. Biophysical analysis reveals that the SYCE2–TEX12 complex is an equimolar hetero-octamer, formed from the association of an SYCE2 tetramer and two TEX12 dimers. Electron microscopy shows that biochemically reconstituted SYCE2–TEX12 complexes assemble spontaneously into filamentous structures that resemble the known physical features of the SC central element (CE). Our findings can be combined with existing biological data in a model of chromosome synapsis driven by growth of SYCE2–TEX12 higher-order structures within the CE of the SC.
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