Related Experiment Video
Updated: Jan 30, 2026

Quantifying Agonist Activity at G Protein-coupled Receptors
Published on: December 26, 2011
Structural Model of Ghrelin Bound to its G Protein-Coupled Receptor
Brian Joseph Bender1, Gerrit Vortmeier2, Stefan Ernicke3
1Department of Pharmacology and Center for Structural Biology, Vanderbilt University, Nashville, TN 37232, USA.
Abstract:
The peptide ghrelin targets the growth hormone secretagogue receptor 1a (GHSR) to signal changes in cell metabolism and is a sought-after therapeutic target, although no structure is known to date. To investigate the structural basis of ghrelin binding to GHSR, we used solid-state nuclear magnetic resonance (NMR) spectroscopy, site-directed mutagenesis, and Rosetta modeling. The use of saturation transfer difference NMR identified key residues in the peptide for receptor binding beyond the known motif. This information combined with assignment of the secondary structure of ghrelin in its receptor-bound state was incorporated into Rosetta using an approach that accounts for flexible binding partners. The NMR data and models revealed an extended binding surface that was confirmed via mutagenesis. Our results agree with a growing evidence of peptides interacting via two sites at G protein-coupled receptors.
Related Concept Videos
G-protein Coupled Receptors
G Protein-coupled Receptors
GPCRs are also called heptahelical, 7TM, or serpentine receptors, and consist of seven (H1-H7) transmembrane alpha-helices that span the bilayer to form a cylindrical core. The transmembrane helices are connected by three extracellular loops and three...
Transducer Mechanism: G Protein–Coupled Receptors
GPCRs are also called heptahelical,...
Protein and Protein Structure
A protein's shape is critical to its function. For example, an enzyme...
Structural Protein Function
Collagen, the most abundant protein in mammals, is found throughout the body. In connective tissue, such as skin, ligaments, and tendons, it provides tensile strength and elasticity. In bones and teeth, it mineralizes to...
Internal Receptors

