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

• Published in: Nature structural & molecular biology Vol. 28; no. 8; pp. 681 - 693
• Main Authors: Dunce, James M., Salmon, Lucy J., Davies, Owen R.
• Format: Journal Article
• Language: English
• Published: New York Nature Publishing Group US 01.08.2021; Nature Publishing Group
• Subjects: 101/28; 631/45/612/100/101; 631/45/612/1228; 631/535/1258; 631/535/1261; 631/535/1266; 82/29; 82/80; 82/83; Biochemistry; Biological Microscopy; Biomedical and Life Sciences; Biophysics; Cell Cycle Proteins - metabolism; Cell research; Cellular proteins; Chromosome Pairing - physiology; Chromosomes; Coils; Crystal structure; Crystallography; Crystallography, X-Ray; Cytoskeletal Proteins - metabolism; Cytoskeleton; Electron microscopy; Elongated structure; Elongation; Fibers; Homology; Humans; Keratin; Keratins - metabolism; Lamins - metabolism; Life Sciences; Long fibers; Meiosis; Meiosis - physiology; Membrane Biology; Microscopy; Mutagenesis; Oligomers; Protein Structure; Protein Structure, Quaternary; Proteins; Self-assembly; Structure; Synaptonemal complex; Synaptonemal Complex - metabolism; Vimentin; Vimentin - metabolism; United Kingdom
• ISSN: 1545-9993; 1545-9985
• DOI: 10.1038/s41594-021-00636-z

The synaptonemal complex (SC) is a supramolecular protein assembly that mediates synapsis between homologous chromosomes during meiosis. SC elongation along the chromosome length (up to 24 μm) depends on its midline α-fibrous component SYCE2-TEX12. Here, we report X-ray crystal structures of human SYCE2-TEX12 as an individual building block and on assembly within a fibrous lattice. We combine these structures with mutagenesis, biophysics and electron microscopy to reveal the hierarchical mechanism of SYCE2-TEX12 fiber assembly. SYCE2-TEX12’s building blocks are 2:2 coiled coils that dimerize into 4:4 hetero-oligomers and interact end-to-end and laterally to form 10-nm fibers that intertwine within 40-nm bundled micrometer-long fibers that define the SC’s midline structure. This assembly mechanism bears striking resemblance with intermediate filament proteins vimentin, lamin and keratin. Thus, SYCE2-TEX12 exhibits behavior typical of cytoskeletal proteins to provide an α-fibrous SC backbone that structurally underpins synaptic elongation along meiotic chromosomes. Crystallographic, electron microscopy and biophysical studies reveal how the synaptonemal complex component SYCE2-TEX12 undergoes self-assembly into fibrous supramolecular structures that mediate homologous chromosome synapsis in meiosis.