Molecular recognition of an acyl-peptide hormone and activation of ghrelin receptor
Ghrelin is a gastric peptide hormone that regulates food intake, body weight, as well as taste sensation, reward, cognition, learning and memory. One unique feature of ghrelin is its acylation, primarily with an octanoic
Ghrelin, also known as “the hunger hormone”, plays a crucial role in regulating various physiological processes. Its multifaceted roles make it a highly attractive drug target for growth retardation, obesity, and metabolic disorders. The binding of ghrelin to its receptor is dependent on the presence of an acyl group, primarily octanoic acid, which is essential for its activation. This study presents two cryo-electron microscopy structures of Gq-coupled ghrelin receptor bound to ghrelin and a synthetic agonist, GHRP-6. Analysis of these structures reveals a unique binding pocket for the acyl group, guiding the correct positioning of the peptide to initiate receptor activation. The findings provide structural templates for drug design targeting ghrelin receptor, offering potential therapeutic avenues for treating related disorders. However, it is essential to note that this research is intended for laboratory use only and not for human clinical applications. As such, peptides synthesized from these structures should be used under the guidance of a qualified professional and in accordance with applicable regulations and safety protocols.