Structural basis of meiotic chromosome synaptic elongation through hierarchical fibrous assembly of SYCE2-TEX12

Dunce, J.M., Salmon, L.J., and Davies, O.R.

Nature Structural & Molecular Biology (2021) 28, 681–693

The synaptonemal complex is a supramolecular assembly that binds together homologous chromosomes during meiosis to facilitate crossing over. Dunce et al show that component complex SYCE2-TEX12 undergoes hierarchical assembly into fibrous structures that support the growth of the synaptonemal complex along the chromosome length.

Summary of Paper by Lori Koch 

Meiosis is the specialised cell division that creates gametes such as egg and sperm. A trademark event in the process is when pairs of homologous chromosomes bind along their lengths, enabling recombination which is the swapping of pieces of DNA between the chromosome inherited from the mother and the chromosome inherited from the father. A large protein complex called the synaptonemal complex physically bridges the chromosomes together. The proteins SYCE2 and TEX12 make up the central element and have been proposed to provide long-range structural support to the synaptonemal complex. In their recent paper in Nature Structure & Molecular Biology, scientists in Owen Davies’ group used X-ray crystallography, SEC-MALS, and electron microscopy (EM) to uncover how SYCE2-TEX12 complexes assemble into fibres. Using SEC-MALS and EM, they found that SYCE2-TEX12 is mainly alpha-helical and forms 2:2, 4:4 and larger complexes in solution but that assembly beyond the 2:2 stage requires the C-terminal tip of TEX12. The stability of the TEX12∆C complex allowed growth of protein crystals which diffracted to 2.42 and 3.33 Angstrom and both 2:2 and 4:4 structures were observed. Given that a 4:4 SYCE2-TEX12∆C complex did not form in solution, the scientists hypothesized that this form was supported by the crystal lattice and so, guided by the structure, they made mutations to the region of TEX12 they hypothesized was important for stabilizing larger complexes. These mutations partially blocked formation of 4:4 complexes and further experiments revealed that an equivalent region at the end of SYCE2 also stabilized 4:4 complexes. Overall, their structural experiments show that in its most basic form SYCE2-TEX12 forms a 2:2 complex which then self-associates into a 4:4. Then, 4:4 complexes assemble via their ends to form 2 and 4 nanometre fibres, which assemble further into 10 nanometre and then 40 nanometre fibres reminiscent of classic intermediate filament proteins.

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