Coiled-coil structure of meiosis protein TEX12 and conformational regulation by its C-terminal tip

• Published in: Communications biology 2022-09, Vol.5 (1), p.921-921, Article 921
• Main Authors: Dunce, James M., Salmon, Lucy J., Davies, Owen R.
• Format: Article
• Language: English
• Subjects: 631/45/535/1261; 631/45/535/1266; 631/45/535/1267; 631/67; 631/80/641/1633; 82/80; 82/83; Biology; Biomedical and Life Sciences; Centrosomes; Chromosomes; Life Sciences; Meiosis; Mutants; Protein structure; Proteins; Synaptonemal complex; X-ray scattering
• ISSN: 2399-3642; 2399-3642
• 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. The X-ray crystal structures of C-terminal mutants of the coiled-coil protein cancer testis antigen TEX12 in combination with modeling of the TEX12 wild-type dimer reveal the protein’s control of its oligomeric state, which resembles assembly of its complex with synaptonemal complex central element protein SYCE2.