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

Lookup NU author(s): Dr Orla Dunne, Dr Owen Davies

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This work is licensed under a Creative Commons Attribution 4.0 International License (CC BY 4.0).


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.


Publication metadata

Author(s): Dunne OM, Davies OR

Publication type: Article

Publication status: Published

Journal: Journal of Biological Chemistry

Year: 2019

Volume: 294

Issue: 23

Pages: 9260-9275

Print publication date: 07/06/2019

Online publication date: 25/04/2019

Acceptance date: 25/04/2019

ISSN (print): 0021-9258

ISSN (electronic): 1083-351X

Publisher: American Society for Biochemistry and Molecular Biology, Inc.

URL: https://doi.org/10.1074/jbc.RA119.008404

DOI: 10.1074/jbc.RA119.008404


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