Extended Data Fig. 4: Comparison of aGPCR structures.
From: Structural basis of tethered agonism of the adhesion GPCRs ADGRD1 and ADGRF1
a, Structural comparison of the CTFs in ADGRD1 and ADGRF1. The receptors in the structures of ADGRD1–miniGs and ADGRF1–miniGs are shown in cartoon representation, and coloured green and blue, respectively. The stalks in the two receptors are coloured orange and magenta, respectively. b–d, Structural comparison of the helical bundles in ADGRD1, ADGRF1 and ADGRG3. The transmembrane helical bundles in the structures of ADGRD1–miniGs and ADGRF1–miniGs and the beclomethasone (BCM)–ADGRG3–Go structure (PDB ID: 7D76) are shown in cartoon representation. b, Extracellular view. The red arrows indicate the movements of helices I, VI and VII in ADGRD1 and ADGRF1 relative to those in ADGRG3. c, Comparison of helix VI conformation. The sharp kink of helix VI in ADGRD1 and ADGRF1 is highlighted by a red dashed box. The palmitoylation in the ADGRG3 structure is shown as grey sticks. d, Intracellular view. The red arrows indicate the movements of helices V and VI in ADGRD1 and ADGRF1 relative to those in ADGRG3. e, Comparison of the G protein-binding cavities in ADGRD1, ADGRF1 and ADGRG3. The receptors in the structures of ADGRD1–miniGs, ADGRF1–miniGs and BCM–ADGRG3–Go are shown in cartoon and surface representations. The α5-helix in Gα is coloured cyan (Gαs) and gold (Gαo). f, Comparison of the Gα α5-helix binding poses in ADGRD1, ADGRF1 and ADGRG3. The structures of ADGRD1–miniGs, ADGRF1–miniGs, ADGRF1–miniGi1 and BCM–ADGRG3–Go are shown in an intracellular view. The red arrow indicates the movement of the C terminus of Gα α5-helix in the ADGRG3 structure relative to that in the ADGRD1 and ADGRF1 structures. g, Comparison of Gs and Gi binding in ADGRF1. The ADGRF1–miniGs and ADGRF1–miniGi1 structures are shown in cartoon representation. The red arrows indicate the movements of the intracellular tip of helix VI, ICL3 and the C terminus of Gα α5-helix in the ADGRF1–miniGs structure relative to those in the ADGRF1–miniGi structure. h, Comparison of the stalk conformation in the ADGRF1 structures. The structures of ADGRF1–miniGs, ADGRF1–miniGi1 and ADGRF1(H565A/T567A)–miniGi1 are shown in an extracellular view. i, Comparison of the binding sites for the stalk in ADGRD1 and ADGRF1 and the ligand glucocorticoid in ADGRG3. The structures of ADGRD1–miniGs, ADGRF1–miniGs and BCM–ADGRG3–Go are shown. The stalk residues FS3, LS6 and MS7 are shown as sticks. The glucocorticoid BCM in the ADGRG3 structure is shown as grey sticks.
