Structure of AMH bound to AMHR2 provides insight into a unique signaling pair in the TGF-β family

Anti-Müllerian hormone (AMH) plays a crucial role in male sex differentiation and female reproductive development. As such, AMH is widely used as a biomarker for measuring a woman's fertility, estimating onset of menopause, and has been implicated in reproductive syndromes such as polycystic ovarian syndrome and premature ovarian failure. Despite its biological relevance, how AMH functions on the molecular level is not well understood. In this study, we show that AMH engages its receptor, AMHR2, using an extensive interface distinct from other type II receptors. Furthermore, we identify several regions in both AMH and AMHR2 that are responsible for specificity and required for AMH signaling.