The synaptonemal complex (SC) is a zipper-like proteinaceous structure that links two homologs together to regulate their recombination and segregation during meiosis. The SC is a tripartite structure comprised of two parallel chromatin-associated axial elements and a central region that connects the paired homologs. Although its role and appearance are highly conserved across eukaryotes, its components have diverged extensively. Moreover, the SC has been refractory to in vitro reconstitution, thus leaving its molecular organization and assembly mechanisms largely mysterious. Recently, we have established that the SC central region in C. elegans is comprised of six coiled-coil proteins, SYP-1, SYP-2, SYP-3 SYP-4, and SYP-5/6, and two Skp1-related proteins, SKR-1 and SKR-2. Remarkably, these proteins form a soluble complex in vitro when co-expressed in bacteria, which we propose to represent a basic building block for SC assembly. Mass photometry has revealed that the SYP/SKR complex has a molecular weight of ∼500 kDa, consistent with a stoichiometry of 2:2:2:2:2:2. Using cross-linking mass spectrometry (XL-MS), we demonstrate that two transverse filament proteins, SYP-1 and SYP-5, form multiple parallel contacts through their elongated coiled-coil domains, while SYP-2 crosslinks exclusively to the N-terminal coiled-coil of SYP-1. Likewise, SYP-3 and SYP-4 make extensive crosslinks within their coiled-coil domains, which link to the N terminus of SYP-1 and both ends of SKR-1. We have visualized the complex using negative stain and found that it forms a 50 nm rod-shaped complex that can polymerize into higher ordered structures. Currently, we are in the process of using this purified complex to obtain its structure using cryo-EM. Our work marks the first successful reconstitution of the complete SC materials in any organism and provides a foundation for deciphering the structure and assembly mechanisms of the SC.
Cesar et al. (2026) studied this question.