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. Author manuscript; available in PMC: 2019 Jul 12.
Published in final edited form as: Cell. 2018 May 24;174(2):312–324.e16. doi: 10.1016/j.cell.2018.04.029

Figure 7.

Figure 7

A longitudinal tunnel in active SMO connects the membrane to the 7TM orthosteric site

(A) Surface of cyclopamine-bound inactive hSMO (yellow, PDB ID: 4O9R). The 7TM cavity is shown in red. See also Figure S7C for the corresponding ribbon model.

(B) As in (A), but showing SANT1-bound inactive hSMO (light blue, PDB ID: 4N4W). Note the remodeling of the 7TM site by SANT1. See also Figure S7D for the corresponding ribbon model.

(C) As in (A), but showing active cyclopamine-bound xSMO (blue). Note the appearance of a tunnel connecting the membrane to the bottom of the 7TM site. See also Figure S7E for the corresponding ribbon model, and Movie S2 for the 360-degree view of the tunnel.

(D) Superimposition of the inactive 7TM cavities for cyclopamine (yellow) and SANT1 (red), and the tunnel (blue).

(E) Close up view of the tunnel in active xSMO, superimposed on inactive cyclopamine-bound hSMO (yellow). Residues that obstruct the tunnel in inactive SMO are shown in sticks. Residue numbers are from hSMO.

(F) As in (E), but showing active cyclopamine-bound xSMO (blue). Movement of the depicted residues opens the tunnel. Residue numbers are from xSMO.

(G) The tunnel superimposed on both inactive (yellow) and active (blue) SMO. Note individual movements of residues involved in tunnel opening upon SMO activation.