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![[Figure 2]](nw5103fig2mag.jpg)
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Figure 2
Structures of agonist-bound, unliganded and antagonist-bound forms. (a, b, c) The crystal structures of (a) agonist (R848)-bound, (b) unliganded and (c) antagonist (CU-CPT8m)-bound forms. A representative image of one protomer is colored blue and the other is colored orange and marked with an asterisk (*). The ligands are represented as ball-and-stick models in which C atoms are represented in yellow, O atoms in red and N atoms in blue. (d, e, f) The overall structures of (d) agonist-bound, (e) unliganded and (f) antagonist-bound forms. The leucine-rich repeat (LRRs) around the ligand-recognition sites are highlighted in purple (LRR8), cyan (LRR11–13), green (LRR15*–16*) and red (LRR17*–18*). The unoccupied pocket is shown by a white dashed rectangle. In the agonist-bound structure, the C-terminal regions are closer than those in the inactivated structures. The antagonist-bound structure was similar to the unliganded structure. (g, h, i) Close-up views around (g) the agonist-bound site (PDB entry 3w3l), (h) the unoccupied pocket (PDB entry 3w3g) and (i) the antagonist-bound site (PDB entry 5wyx). The chemical structure of each ligand is shown below the close-up view. Interactions of the agonist involve hydrophobic residues such as Phe346, Tyr348, Gly376, Val378, Ile403–Phe405, Val520*, Asp543*, Gly572*–Thr574* and some hydrogen bonds. Interactions of the antagonist involve hydrophobic residues such as Phe261, Phe346, Val378, Ile403, Phe405, Phe494*, Ala518*, Val520* and Tyr567*, stacking interactions with Tyr348 and Phe495* and some hydrogen bonds. LRR11–13 confront LRR15*–16* in the unliganded structure and the antagonist-bound structure, while LRR11–13 mainly interact with LRR17*–18* in the agonist-bound structure. |
![[Figure 2]](nw5103fig2.jpg)
 | STRUCTURAL BIOLOGY |
ISSN: 2059-7983
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