An atomic look at the interface of GHSR and its partners

G protein-coupled receptors (GPCRs) regulate cellular activity by transducing external signals and selectively coupling them to intracellular partners. Ghrelin receptor (GHSR) has garnered significant interest over the past decade owing to its diverse functional roles. In this study, we simulated five distinct GHSR-partner complexes, including G_q, G_i, and arrestin in two conformational states, to investigate the structural determinants of partner coupling. Interface and contact analyses revealed conserved interaction sites and novel interactions that were specific to each partner family. Molecular dynamics simulations provided insights into GHSR conformational dynamics, highlighting notable differences in key structural regions across complexes, such as the TM5 bulge. Our findings underscore the structural diversity of GHSR coupling mechanisms and contribute to a deeper understanding of their functional versatility.