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

Nat Struct Mol Biol. 2021 Aug;28(8):681-693. doi: 10.1038/s41594-021-00636-z. Epub 2021 Aug 9.

Abstract

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.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Cell Cycle Proteins / metabolism*
  • Chromosome Pairing / physiology*
  • Crystallography, X-Ray
  • Cytoskeletal Proteins / metabolism
  • Humans
  • Keratins / metabolism
  • Lamins / metabolism
  • Meiosis / physiology
  • Protein Structure, Quaternary
  • Synaptonemal Complex / metabolism*
  • Vimentin / metabolism

Substances

  • Cell Cycle Proteins
  • Cytoskeletal Proteins
  • Lamins
  • TEX12 protein, human
  • Vimentin
  • Keratins