Fig. 6: Conformational dynamics of a class B1 GPCR.
From: Impact of secretin receptor homo-dimerization on natural ligand binding
Conformational dynamics of the active, Gs protein-coupled, GLP-1 receptor bound with agonist analog, semaglutide, provide a potential model for the shifts in cysteine cross-linking patterns of WT and non-dimerizing mutant SecR. This shows cryo-EM data of semaglutide bound to GLP-1R25, showing focused refinement map and model (left, pink) and map and model of principal component 0 (PCA0) of the CryoSPARC 3D variability analysis (3DVA) (middle, blue), as well as an overlay of both models (right). In the closed conformation (left panel) the semaglutide peptide is proximal to ECL2 and ECL3, similar to the conformation of the active, monomeric SecR-secretin structure and pattern of cysteine cross-linking at the non-dimerizing SecR suggested by the current work. Outward movement of ECL3 is accompanied by a translation of the semaglutide peptide (middle and right panels) that moves away from ECL2, but remains proximal to ECL3, consistent with the pattern of cysteine cross-linking observed at the WT (dimer competent) SecR.
