Author(s) :

Anvee Sharma.

Volume/Issue :

Abstract :

Meiosis is an essential process for gametogenesis and fertility, requiring a network of proteins that coordinate homologous chromosome pairing, synapsis, and recombination. The HORMA domaincontaining protein HORMAD1 plays a key role in these events by localizing to unsynapsed chromosomal axes, promoting synaptonemal complex formation, and activating meiotic checkpoints. Disruptions in HORMAD1 function have been linked to infertility, yet the molecular basis of its interactions and regulation remains incompletely understood. In this study, AlphaFold was used to investigate how HORMAD1 recognizes its own closure motif and interacts with known meiotic partners. Validation with canonical and mutant peptides confirmed that AlphaFold accurately predicts established binding behaviors. Screening of potential closure motif–like sequences revealed novel candidate interactions with MCM9, SYNP2, and ATR, while IHO1 and BRCA1 showed minimal binding confidence. Additionally, modeling of phosphorylated peptides suggested that posttranslational modification can disrupt HORMAD1’s autoinhibitory conformation and regulate its interactions with other meiotic factors, potentially regulating its activity during meiosis. These findings demonstrate that AlphaFold can recapitulate known biochemical results and predict new interaction candidates, providing a structural framework for future experimental validation. Understanding HORMAD1’s binding specificity and regulation advances insight into the molecular mechanisms underlying meiotic control and fertility disorders.