Extended Data Fig. 5: Conformational changes in CB1 activation.
From: Molecular mechanism of allosteric modulation for the cannabinoid receptor CB1
(a) Comparison of the active state CB1 bound agonist AM841 (salmon, PDB: 6KPG) with the inactive state CB1 bound antagonist AM6538 (slate, PDB: 5TGZ) reveals that the intracellular end of the TM6 helix moves outward significantly. (b) The upward rearrangement of TM3 upon CB1 activation (salmon, PDB: 6KPG). (c) The extracellular end of TM2 has inward movement, and its intracellular end is found to have downward rotation along the helical axis when comparing with inactive state of CB1 (slate, PDB: 5TGZ). In particular, F1552.42 undergoes a major conformational transition during receptor activation. (d) Structural superimposition reveals that the extracellular ends of TM1 and TM2 move into the core of helical bundles.
