Fig. 4.

Model for sterol regulation of Smo activity. (A) Ptc, which is structurally related to transporter and pump proteins, may inhibit Smo by pumping activating sterols away from Smo. In the presence of Shh or in the genetic absence of Ptc, sterols would be free to directly promote Smo activity. (B) Sterols may activate Smo by direct binding. In the absence of sterols, Smo remains in an inactive conformation. When sterols are present, they may bind to Smo, causing an activating conformational change. CPN may compete with sterols for binding to Smo by virtue of the structural similarity of CPN and sterols. Binding of CPN to Smo would stabilize the inactive conformation.