7RTB
Peptide-19 bound to the Glucagon-Like Peptide-1 Receptor (GLP-1R)
Summary for 7RTB
| Entry DOI | 10.2210/pdb7rtb/pdb |
| EMDB information | 24680 |
| Descriptor | Guanine nucleotide-binding protein G(s) subunit alpha isoforms short, Guanine nucleotide-binding protein G(I)/G(S)/G(T) subunit beta-1, Guanine nucleotide-binding protein G(I)/G(S)/G(O) subunit gamma-2, ... (7 entities in total) |
| Functional Keywords | glucagon-like peptide-1 receptor (glp-1r), peptide-19 cryo-em, membrane protein |
| Biological source | Homo sapiens (Human) More |
| Total number of polymer chains | 6 |
| Total formula weight | 163991.76 |
| Authors | Johnson, R.M.,Danev, R.,Sexton, P.M.,Wootten, D. (deposition date: 2021-08-12, release date: 2021-10-06) |
| Primary citation | Johnson, R.M.,Zhang, X.,Piper, S.J.,Nettleton, T.J.,Vandekolk, T.H.,Langmead, C.J.,Danev, R.,Sexton, P.M.,Wootten, D. Cryo-EM structure of the dual incretin receptor agonist, peptide-19, in complex with the glucagon-like peptide-1 receptor. Biochem.Biophys.Res.Commun., 578:84-90, 2021 Cited by PubMed Abstract: Dual agonists that can activate both the glucagon-like peptide-1 receptor (GLP-1R) and the gastric inhibitory polypeptide receptor (GIPR) have demonstrated high efficacy for the treatment of metabolic disease. Peptide-19 is a prototypical dual agonist that has high potency at both GLP-1R and GIPR but has a distinct signalling profile relative to the native peptides at the cognate receptors. In this study, we solved the structure of peptide-19 bound to the GLP-1R in complex with Gs protein, and compared the structure and dynamics of this complex to that of published structures of GLP-1R:Gs in complex with other receptor agonists. Unlike other peptide-bound receptor complexes, peptide-19:GLP-1R:Gs demonstrated a more open binding pocket where transmembrane domain (TM) 6, TM7 and the interconnecting extracellular loop 3 (ECL3) were located away from the peptide, with no interactions between peptide-19 and TM6/ECL3. Analysis of conformational variance of the complex revealed that peptide-19 was highly dynamic and underwent binding and unbinding motions facilitated by the more open TM binding pocket. Both the consensus structure of the GLP-1R complex with peptide-19 and the dynamics of this complex were distinct from previously described GLP-1R structures providing unique insights into the mode of GLP-1R activation by this dual agonist. PubMed: 34547628DOI: 10.1016/j.bbrc.2021.09.016 PDB entries with the same primary citation |
| Experimental method | ELECTRON MICROSCOPY (2.14 Å) |
Structure validation
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