Extended Data Fig. 6: Structural superpositions with the nAChR α4β2, the GABA_A receptor β3 subunit and the apo 5-HT₃ receptor structures.

a, Putty representations of pairwise deviations for the 5-HT₃ receptor conformations. The selection used for superimposition, and the two conformations used, are noted for each image. The colour code and tube thickness code are the same for all images. In the T versus X-ray image, the red zone corresponds to a loop that was not modelled in the X-ray structure. b, Superimposition of a 5-HT₃ receptor subunit in the inhibited T state (blue) and of a 5-HT₃ receptor subunit in the apo state (grey, PDB: 6BE1). Structures are globally similar with differences in the lipid-exposed helices M3, MX and M4, hypothetically a consequence of the different additives used—a lipid mixture in this study versus fluorinated fos-choline 8 for the apo structure. Superposition of the T structure (blue), the apo structure (grey) and the X-ray structure (orange). c, Superposition of a 5-HT₃ receptor subunit in the I1, I2 and F conformations with a nAChR α4 subunit (PDB: 5KXI, chain A) or a GABA_A receptor β3 subunit (PDB: 4COF). C_α r.m.s.d. is noted. Comparison of superpositions with r.m.s.d. below 2 Å shows that in the case of F and nAChR α4 (middle, purple and grey), the domain-to-domain orientation is very similar and the extracellular halves of helices M1, M2, M3 superimpose very well, whereas clear deviations are present in their intracellular halves and at the level of M4 (r.m.s.d. without M4 drops to 1.6 Å). In the case of I1 and GABA_A β3 (left, yellow and black), or I2 and GABA_A β3 (right, green and black), differences are more distributed; deviations of the ECD indicate different domain-to-domain orientations, and in the TMD M1 and M3 superimpose quite well but M2 and M4 clearly differ.