Structural insight into ligand binding and activation of the orphan GPCR Mas1 - PubMed
7 hours ago
- #GPCR
- #Structural Biology
- #Cryo-EM
- Cryo-EM structures reveal Mas1 bound to agonists NPFF and AR234958 with inhibitory G proteins.
- Mas1 uses a non-canonical activation mechanism involving a hydrophobic compression plane, not the W6.48 toggle switch.
- Key residues identified: Y2486.55, L872.60, I842.57, L2667.39 for ligand binding; M2446.51 and F2376.44 as molecular switches.
- Structural analysis compares Mas1 to MRGPRX1-X4, showing conserved and divergent features within the subfamily.
- Findings provide a framework for understanding Mas1 pharmacology and designing selective therapeutics.