Molecular architecture of the SYCP3 fibre and its interaction with DNA

Abstract

The synaptonemal complex (SC) keeps homologous chromosomes in close alignment during meiotic recombination. A hallmark of the SC is the presence of its constituent protein SYCP3 on the chromosome axis. During SC assembly, SYCP3 is deposited on both axes of the homologue pair, forming axial elements that fuse into the lateral element (LE) in the tripartite structure of the mature SC. We have used cryo-electron tomography and atomic force microscopy to study the mechanism of assembly and DNA binding of the SYCP3 fibre. We find that the three-dimensional architecture of the fibre is built on a highly irregular arrangement of SYCP3 molecules displaying very limited local geometry. Interaction between SYCP3 molecules is driven by the intrinsically disordered tails of the protein, with no contact between the helical cores, resulting in a flexible fibre assembly. We demonstrate that the SYCP3 fibre can engage in extensive interactions with DNA, indicative of an efficient mechanism for incorporation of DNA within the fibre. Our findings suggest that SYCP3 deposition on the chromosome axis might take place by polymerization into a fibre that is fastened to the chromosome surface via DNA binding.

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

“…This enabled the X-ray crystallographic structure solution of SYCE2-TEX12’s minimum structural unit, a 2:2 complex, revealing an unusual three- and four-helical bundle fold in which TEX12 chains are positioned with their C-termini at either end of the rod-like structure of 20-nm length and 2-nm width. We propose that the 2:2 complex is SYCE2-TEX12’s obligate structure that constitutes its minimum building-block for assembly into 4:4 complexes and fibres, and is comparable to the obligate tetramers of SYCP1 and SYCP3 that act as building-blocks for their respective assembly into lattice-like assays and paracrystalline fibres (Dunce et al, 2018a, Syrjanen et al, 2014, Bollschweiler et al, 2019).…”

“…Thus, the intermediate filament-like nature of SYCE2-TEX12 fibres provides longitudinal strength and a single longitudinal axis to underpin the generation of a single continuous SC from discrete inter-homologue recombination events. Similarly, SYCP1 and SYCP3 assemblies have defined roles in the physical tethering of axes and stabilising compacted looped chromatin structure, respectively (Dunce et al, 2018a, Syrjanen et al, 2017, Syrjanen et al, 2014, Bollschweiler et al, 2019). Thus, we conclude that the SC’s subcomplexes and components, including SYCP1, SYCP3 and SYCE2-TEX12, form unique supramolecular assemblies which provide distinct functionalities that are combined in a modular manner through interactions with other SC proteins to achieve the enigmatic structural and functional roles of the SC in meiosis.…”

“…SYCP1 is a tetramer that assembles into a lattice-like array to fulfil the fundamental role of the SC in tethering chromosome axes (Dunce et al, 2018a). SYCP3 is a tetramer that assembles into paracrystalline fibres, which have been observed for the recombinant protein in vitro (Syrjanen et al, 2014, Bollschweiler et al, 2019, upon heterologous cellular expression (Yuan et al, 1998, Baier et al, 2007a, Baier et al, 2007b, and in the native mammalian SC (Ortiz et al, 2002). SYCP3 fibres separate DNA-binding sites by a 23 nm repeating unit along the longitudinal axis, which facilitates the compaction of chromatin loops within the meiotic chromosome axis (Syrjanen et al, 2014).…”

“…In the last decade, the molecular underpinning of the SC has started to come into focus through analysis of SC proteins by structural biology (Syrjanen et al, 2014, Lu et al, 2014, Syrjanen et al, 2017, Dunce et al, 2018a, Dunne and Davies, 2019a, Dunne and Davies, 2019b, West et al, 2019, Sanchez-Saez et al, 2020, Bollschweiler et al, 2019). An emerging theme is that SC proteins, which are almost universally coiled-coils, exist as defined building-blocks that can self-assemble into large molecular weight structures to provide the SC’s distinct architectural elements.…”

Copy number variants and fixed duplications among 198 rhesus macaques (Macaca mulatta)

“…Heterozygous mutations in this gene have been associated with male infertility [72]. This mutation truncates the protein and reduces the ability to interact with the wild type protein probably affecting SYCP3 fibre formation, which can engage in extensive interactions with DNA [73]. As this mutation has been suggested to compromise spermatogenesis via a dominant negative interference, the additional copy in rhesus macaques may make them more susceptible to this disorder (although it might result in a milder condition).…”