Biosciences Institute, Faculty of Medical Sciences, Newcastle University, Framlington Place, Newcastle upon Tyne, NE2 4HH, UK.
Department of Biochemistry, University of Cambridge, 80 Tennis Court Road, Old Addenbrookes Site, Cambridge, CB2 1GA, UK.
Commun Biol. 2022 Sep 7;5(1):921. doi: 10.1038/s42003-022-03886-9.
Meiosis protein TEX12 is an essential component of the synaptonemal complex (SC), which mediates homologous chromosome synapsis. It is also recruited to centrosomes in meiosis, and aberrantly in certain cancers, leading to centrosome dysfunction. Within the SC, TEX12 forms an intertwined complex with SYCE2 that undergoes fibrous assembly, driven by TEX12's C-terminal tip. However, we hitherto lack structural information regarding SYCE2-independent functions of TEX12. Here, we report X-ray crystal structures of TEX12 mutants in three distinct conformations, and utilise solution light and X-ray scattering to determine its wild-type dimeric four-helical coiled-coil structure. TEX12 undergoes conformational change upon C-terminal tip mutations, indicating that the sequence responsible for driving SYCE2-TEX12 assembly within the SC also controls the oligomeric state and conformation of isolated TEX12. Our findings provide the structural basis for SYCE2-independent roles of TEX12, including the possible regulation of SC assembly, and its known functions in meiotic centrosomes and cancer.
减数分裂蛋白 TEX12 是联会复合体（SC）的重要组成部分，介导同源染色体联会。它也在减数分裂中被招募到中心体，并且在某些癌症中异常，导致中心体功能障碍。在 SC 内，TEX12 与 SYCE2 形成一个相互交织的复合物，通过 TEX12 的 C 末端尖端进行纤维组装。然而，我们目前缺乏关于 TEX12 非依赖性功能的结构信息。在这里，我们报告了三种不同构象的 TEX12 突变体的 X 射线晶体结构，并利用溶液光散射和 X 射线散射来确定其野生型二聚体四螺旋卷曲螺旋结构。TEX12 在 C 末端尖端突变后发生构象变化，表明负责在 SC 内驱动 SYCE2-TEX12 组装的序列也控制着分离的 TEX12 的寡聚状态和构象。我们的发现为 TEX12 的 SYCE2 非依赖性作用提供了结构基础，包括对 SC 组装的可能调节，以及其在减数分裂中心体和癌症中的已知功能。
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