A molecular model for self-assembly of the synaptonemal complex protein SYCE3

Orla M. Dunne, Owen R. Davies

Research output: Contribution to journalArticlepeer-review

Abstract / Description of output

The synaptonemal complex (SC) is a supramolecular protein assembly that mediates homologous chromosome synapsis during meiosis. This zipper-like structure assembles in a continuous manner between homologous chromosome axes, enforcing a 100-nm separation along their entire length and providing the necessary three-dimensional framework for cross-over formation. The mammalian SC comprises eight components—synaptonemal complex protein 1–3 (SYCP1–3), synaptonemal complex central element protein 1–3 (SYCE1–3), testis-expressed12 (TEX12), and six6 opposite strand transcript 1 (SIX6OS1)—arranged in transverse and longitudinal structures. These largely -helical, coiled-coil proteins undergo heterotypic interactions, coupled with recursive self-assembly of SYCP1,SYCE2–TEX12, and SYCP2–SYCP3, to achieve the vast supramolecular SC structure. Here, we report a novel self-assembly mechanism of the SC central element component SYCE3, identified through multi-angle light scattering and small-angle X-ray scattering (SAXS) experiments. These analyses revealed thatSYCE3 adopts a dimeric four-helical bundle structure that acts as the building block for concentration-dependent self-assembly in to a series of discrete higher-order oligomers. We observed that this is achieved through staggered lateral interactions between self-assembly surfaces of SYCE3 dimers and through end-on interactions that likely occur through intermolecular domain swapping between dimer folds. These mechanisms are combined to achieve potentially limitless SYCE3 assembly, particularly favoring formation of dodecamers of three laterally associated end-on tetramers. Our findings extend the family of self-assembling proteins within the SC and reveal additional means for structural stabilization of the SC central element.
Original languageEnglish
Pages (from-to)9260-9275
Number of pages16
JournalJournal of Biological Chemistry
Volume294
Issue number23
DOIs
Publication statusPublished - 7 Jun 2019

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