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bioRxiv · 10.64898/2026.06.03.730022

Assembly principles of a SYCP2-HORMAD1-HORMAD2 mammalian meiotic axis complex

Selezneva, E.·Mueller, F.·Janning, P.·Weir, J. R.
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Abstract

During meiotic prophase I, the chromosome axis orchestrates programmed DNA double-strand break formation, repair and synapsis between homologous chromosomes. In mammals, the axis is assembled from the coiled-coil elements SYCP2 and SYCP3 that come together with the HORMA-domain proteins HORMAD1 and HORMAD2, but how these components associate into a coherent structural unit remains incompletely understood. Combining recombinant reconstitution, mass photometry, SEC-MALS, AlphaFold modelling and crosslinking mass spectrometry, we show that the HORMA domains of HORMAD1 and HORMAD2 form a selective pseudosymmetric heterodimer independently of either proteins own closure motif, with interface determinants conserved across vertebrates. We identify a previously unrecognised second closure motif (CM2) in SYCP2 that preferentially binds HORMAD1, distinct from the previously described HORMAD2-binding closure motif (CM1). Together, these results revise the current model of mammalian axis assembly and define a tripartite SYCP2-HORMAD1-HORMAD2 module as a fundamental structural unit of the mammalian meiotic chromosome axis.

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Selezneva, E., Mueller, F., Janning, P., Weir, J. R.. 2026-06-08. Assembly principles of a SYCP2-HORMAD1-HORMAD2 mammalian meiotic axis complex. https://doi.org/10.64898/2026.06.03.730022

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