Extended Data Fig. 9: Ligand binding mode comparison in different cmpd644-bound APJR structures reported in this study.

a, The crystal packing, SEC profile and crystal images from 112 crystals of _xtalAPJR^cmpd644. b, Structural alignment of cytoplasmic portion of TM5/6/7 in the _xtalAPJR^cmpd644 structure (gray) suggested inactive conformation when compared to inactive-state AMG3054-APJR co-crystal structure (PDB ID: 5VBL, green) and active-state ProtA in _dimAPJR^cmpd644–Gi complex (blue). c, Comparison of binding pockets between cmpd644 (yellow) in ProtA (blue) and AMG3054 (purple) in APJR co-crystal structure (green). Related residues are shown in sticks. Dashed lines circled the dimethoxyphenyl group of cmpd644 that mimics the phenyl ring of F17 in AMG3054. d, Extended interactions of cmpd644 with _xtalAPJR in the subpocket. Interacting residues of APJR are shown as sticks in pink. e, Structural comparison of the residues in the ligand binding pocket (left) or underneath (right). Conformational changes of key residues in the active-state ProtA (blue) from that of inactive-state _xtalAPJR (gray) are indicated. f, Orthogonal views of superimposed cmpd644 in ProtA (yellow), _monAPJR (green) and _xtalAPJR^cmpd644 structures (orange), respectively. _xtalAPJR is shown as surface in gray. g, Cmpd644 binding pocket superposition between ProtA (blue) and _monAPJR (purple). Cmpd644 are shown as yellow and cyan, respectively. h, Superposition of cmpd644 and comparison of cmpd644 binding pockets between ProtA (blue) and ProtB (gray). Cmpd644 are shown as yellow and pink, respectively. Related residues are presented as sticks and dashed lines represent hydrogen bonds.