Molecular structure of human synaptonemal complex protein SYCE1

Orla M Dunne,Owen R Davies

doi:10.1007/s00412-018-00688-z

Abstract

The reduction in chromosome number during meiosis is essential for the production of haploid germ cells and thereby fertility. To achieve this, homologous chromosomes are first synapsed together by a protein assembly, the synaptonemal complex (SC), which permits genetic exchange by crossing over and the subsequent accurate segregation of homologues. The mammalian SC is formed of a zipper-like array of SYCP1 molecules that bind together homologous chromosomes through self-assembly in the midline that is structurally supported by the central element. The SC central element contains five proteins—SYCE1, SYCE3, SIX6OS1, and SYCE2-TEX12—that permit SYCP1 assembly to extend along the chromosome length to achieve full synapsis. Here, we report the structure of human SYCE1 through solution biophysical methods including multi-angle light scattering and small-angle X-ray scattering. The structural core of SYCE1 is formed by amino acids 25–179, within the N-terminal half of the protein, which mediates SYCE1 dimerization. This α-helical core adopts a curved coiled-coil structure of 20-nm length in which the two chains are arranged in an anti-parallel configuration. This structure is retained within full-length SYCE1, in which long C-termini adopt extended conformations to achieve an elongated molecule of over 50 nm in length. The SYCE1 structure is compatible with it functioning as a physical strut that tethers other components to achieve structural stability of the SC central element.

Highlights

The challenging task of generating haploid germ cells by meiosis is achieved through a series of molecular events, coupled with structural and topological changes to chromosomes that result in homologous chromosome segregation following genetic exchange by crossing over (Hunter 2015; Loidl 2016; Zickler and Kleckner 2015)
The assembly of a structurally and functionally mature synaptonemal complex (SC) is dependent on SC central element proteins SYCE1–3, TEX12, and SIX6OS1 (Bolcun-Filas et al 2007; Bolcun-Filas et al 2009; Gomez et al 2016; Hamer et al 2008; Schramm et al 2011), which are thought to stabilise the underlying SYCP1 lattice to permit its synaptic extension along the length of meiotic chromosomes (Dunce et al 2018)
The SYCE1 structural core, formed by an N-terminal region of amino acids 25–179, is an α-helical dimer that adopts an anti-parallel Bcoiled-coil^-like structure of approximately 20 nm in length

Summary

Introduction

The challenging task of generating haploid germ cells by meiosis is achieved through a series of molecular events, coupled with structural and topological changes to chromosomes that result in homologous chromosome segregation following genetic exchange by crossing over (Hunter 2015; Loidl 2016; Zickler and Kleckner 2015). The three-dimensional structure of the SC physically tethers together homologous chromosomes and facilitates recombination intermediate resolution, with the formation of typically one crossover per chromosome arm (Zickler and Kleckner 2015). Crossovers provide the sole physical links between homologues at metaphase I, with their subsequent segregation triggered by arm cohesin cleavage. These intricate molecular processes are essential for meiotic division and fertility in mice (Hopkins et al 2014; Horn et al 2013; Kouznetsova et al 2011; Shibuya et al 2015), and their defective function

Methods

Results

Conclusion