Structural maturation of SYCP1-mediated meiotic chromosome synapsis through conformational remodelling by molecular adapter SYCE3
Structural maturation of SYCP1-mediated meiotic chromosome synapsis through conformational remodelling by molecular adapter SYCE3
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DOI：
10.1101/2022.03.06.483192
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发表时间：
2022-03
期刊：
影响因子：
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通讯作者：
James H. Crichton;J. M. Dunce;O. Dunne;L. Salmon;Paul S. Devenney;J. Lawson;I. Adams;O. Davies
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文献类型：
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作者：
James H. Crichton;J. M. Dunce;O. Dunne;L. Salmon;Paul S. Devenney;J. Lawson;I. Adams;O. Davies
在减数分裂中，一种超分子蛋白质结构，联会复合体(SC)，在同源染色体之间组装，以促进它们的重组。哺乳动物SC的形成被认为涉及SYCP1蛋白质晶格的分层拉链状组装，当SYCP1蛋白质晶格延伸时，它招募稳定的中央元件(CE)蛋白质。在这里，我们将生化方法与小鼠的功能分离突变相结合，以发现CE蛋白SYCE3在突触过程中主动重塑这一结构，而不是稳定SYCP1晶格。我们发现，SYCP1四聚体在SYCE3结合后发生构象变化，变成2：1的杂三聚体，移除了它们的组装界面，破坏了SYCP1的晶格。然后，SYCE3通过自组装建立一个新的晶格，模仿被破坏的界面在连接SYCP1二聚体中的作用。SYCE3还与CE络合物SYCE1-SIX6OS1和SYCE2-TEX12相互作用，为它们的招募提供了一种机制。因此，SYCE3将SYCP1晶格重塑为CE结合的整合SYCP1-SYCE3晶格，以实现成熟SC的远程突触。
In meiosis, a supramolecular protein structure, the synaptonemal complex (SC), assembles between homologous chromosomes to facilitate their recombination. Mammalian SC formation is thought to involve hierarchical zipper-like assembly of an SYCP1 protein lattice that recruits stabilising central element (CE) proteins as it extends. Here, we combine biochemical approaches with separation-of-function mutagenesis in mice to uncover that, rather than stabilising the SYCP1 lattice, the CE protein SYCE3 actively remodels this structure during synapsis. We find that SYCP1 tetramers undergo conformational change into 2:1 heterotrimers upon SYCE3-binding, removing their assembly interfaces and disrupting the SYCP1 lattice. SYCE3 then establishes a new lattice by its self-assembly mimicking the role of the disrupted interface in tethering together SYCP1 dimers. SYCE3 also interacts with CE complexes SYCE1-SIX6OS1 and SYCE2-TEX12, providing a mechanism for their recruitment. Thus, SYCE3 remodels the SYCP1 lattice into a CE-binding integrated SYCP1-SYCE3 lattice to achieve long-range synapsis by a mature SC.