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

Abstract

The supramolecular structure of the synaptonemal complex (SC) mediates homologous chromosome synapsis and facilitates the formation of genetic crossovers during meiosis. The mammalian SC is formed of eight coiled-coil proteins which interact in specific subcomplexes and self-assemble into distinct macromolecular arrays that fulfil specific aspects of the SC’s dynamic functional architecture. Here, we report the structure of SC subcomplex SYCE2-TEX12 and its mechanism of self-assembly into fibres that define the SC’s midline longitudinal structure. X-ray crystal structures, electron microscopy, biophysical and mutational analyses reveal that SYCE2-TEX12 is assembled from 2:2 complexes in which TEX12 chains are positioned at either end of a rod-like SYCE2 dimer. These molecular building-blocks assemble laterally into 4:4 complexes, and longitudinally into fibres of potentially limitless length, which acts as string-like threads that wind around one another in intertwined fibres of up to 40-nm in width and several micrometres in length. This hierarchical assembly mechanism is reminiscent of intermediate filament proteins and results in SYCE2-TEX12 fibres that can span the entire chromosome length, thereby providing the underpinning structural support for SC elongation during meiotic chromosome synapsis.

The Zip4 protein directly couples meiotic crossover formation to synaptonemal complex assembly

“…S7). This coevolution pattern is fully consistent with the structure of the SYCE2-TEX12 hetero-tetramer (Dunce et al, 2021) (Fig. 6C).…”

“…The copyright holder for this preprint this version posted August 13, 2021. ; https://doi.org/10.1101/2021.08.13.456249 doi: bioRxiv preprint human TEX12 and its close interacting partner, SYCE2, have been solved (PDB: 6R17) (Figure 6C) (Davies et al, 2012;Dunce et al, 2021). TEX12 is predicted to be SUMOylated on lysine 8, located at the very N-terminal extremity of the protein (see Materials and Methods), similarly to Ecm11 SUMOylation at lysine 5 (Humphryes et al, 2013).…”

“…This suggests that the interaction between the ZMM protein Zip4/TEX11 and the central element of the SC may be conserved, and that TEX12 may be a functional homolog of Ecm11. The three-dimensional structures of human TEX12 and its close interacting partner, SYCE2, have been solved (PDB: 6R17) (Figure 6C) (Davies et al, 2012;Dunce et al, 2021). TEX12 is predicted to be SUMOylated on lysine 8, located at the very N-terminal extremity of the protein (see Materials and Methods), similarly to Ecm11 SUMOylation at lysine 5 (Humphryes et al, 2013).…”

Centrosome dysfunction associated with somatic expression of the synaptonemal complex protein TEX12

“…4d, e and Supplementary Fig. 3e, f ), corresponding to the same region that interacts with SYCE2 30 . Thus, TEX12 can adopt alternative conformations of an isolated homodimer or within 2:2, 4:4 and fibrous SYCE2:TEX12 complexes, through the same α-helical core.…”

Predicting direct physical interactions in multimeric proteins with deep learning

“…2 displays the results of AF2Complex predictions on some challenging targets. The first example, H1072, is an A2B2 heterotetramer consisting of two copies of two coiled-coil protein sequences [37] (The subscripted numbers indicate the stoichiometry if unequal to one). Despite the simple topologies adopted by the individual monomers and the availability of an experimental structure for one monomer, H1072 is a difficult target.…”