Mutational analysis of the putative Anti-M üllerian Hormone (AMH) binding interface on its type II receptor, AMHR2.

In this study, we used previous structural information to derive a model of AMH bound to AMHR2 to guide mutagenesis studies to identify receptor residues important for AMH signaling. Non-conserved mutations were introduced in AMHR2 and characterized in an AMH responsive cell-based luciferase assay and Native PAGE. Collectively, our results identified several residues important for AMH signaling within the putative ligand binding interface of AMHR2. Our results show that AMH engages AMHR2 at a similar interface to how Activin and BMP class ligands bind the type II receptor, ACVR2B, however, there are significant molecular differences at the ligand interface of these two receptors, where ACVR2B is mostly hydrophobic and AMHR2 is predominately charged. Overall, this study shows that while the location of ligand binding on the receptor is similar to ACVR2A, ACVR2B, and BMPR2; AMHR2 uses unique ligand-receptor interactions to impart specificity for AMH. PMID: 32333774 [PubMed - as supplied by publisher]
Source: Endocrinology - Category: Endocrinology Authors: Tags: Endocrinology Source Type: research