Extended Data Figure 15. Alignment of all known 5-HT2A Structures.
(a) All of the 5-HT2A structures were downloaded from the PDB and aligned via matchmaker in ChimeraX. Shown is the orthosteric pocket (and Z7757) with residues highlighted which showed the biggest differences between the two docking models. The structures are colored by method of determination AF2-model in cyan, cryoEM structures in cornflower blue, and crystal structures in grey. (b) Highlighted structural differences to show that a cryoEM structure can adopt the closed off pose of W1513.28 exhibited by the AF2-model. Here the AF2-model is shown in cyan, Z7757 cryoEM structure is shown in cornflower blue, the Lisuride cryoEM structure is shown in dark purple, and the agonist R-69 (PDB: 7RAN) cryoEM structure is shown in salmon. (c) Showing that an antagonist crystal structure can also adopt the closed position of W1513.28 exhibited by the AF2-model. Here the AF2-model is shown in cyan, Z7757 cryoEM structure is shown in cornflower blue, the Lisuride cryoEM structure is shown in dark purple, and the antagonist Zotepine (PDB: 6A94) cryoEM structure is shown in grey.