Publication

Article Metrics

Citations


Online attention

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

DOI: 10.1074/jbc.RA119.008404 DOI Help

Authors: Orla M. Dunne (Newcastle University) , Owen R. Davies (Newcastle University)
Co-authored by industrial partner: No

Type: Journal Paper
Journal: Journal Of Biological Chemistry

State: Published (Approved)
Published: April 2019
Diamond Proposal Number(s): 14435 , 15580 , 15836 , 15897

Open Access Open Access

Abstract: 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 crossover formation. The mammalian SC comprises eight components—synaptonemal complex protein 1–3 (SYCP1–3), synaptonemal complex central element protein 1–3 (SYCE1–3), testis expressed 12 (TEX12), and six6 opposite strand transcript 1 (SIX6OS1)—arranged in transverse and longitudinal structures. These largely α-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 that SYCE3 adopts a dimeric four-helical bundle structure that acts as the building block for concentration-dependent self-assembly into 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.

Journal Keywords: Synaptonemal complex; SYCE3; Coiled-coil; Domain-swap; structural biology; molecular modeling; meiosis; protein self-assembly; biophysics; chromatin structure; small-angle X-ray scattering (SAXS)

Subject Areas: Biology and Bio-materials, Medicine


Instruments: B21-High Throughput SAXS