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. Author manuscript; available in PMC: 2019 Dec 24.
Published in final edited form as: Curr Opin Struct Biol. 2019 Jun 24;57:204–214. doi: 10.1016/j.sbi.2019.05.015

Figure 1. Transmission of the Hedgehog (HH) signal across the plasma membrane.

Figure 1

(a) The receptor for HH ligands, PTCH1 (a 12-pass TM protein) inhibits SMO (a 7-pass TM protein) and thereby prevents it from initiating signalling in the cytoplasm of target cells. The domain architecture of both TM proteins is highlighted. PTCH1 is composed of two tandem RND (resistance-nodulation-division) domains: ECD1, extracellular domain 1; ECD2, extracellular domain 2; NTD, N-terminal domain; CTD, C-terminal domain; ICL3, intracellular loop 3; SSD, sterol-sensing domain (light blue). SMO is composed of an extracellular region which is made up of a cysteine rich domain (CRD) and linker domain (LD) followed by a 7-pass transmembrane bundle characteristic of GPCRs and then a unique intracellular domain (ICD). (b) HH ligands (such as Sonic Hedgehog (SHH)) bind and inhibit PTCH1, allowing SMO activation, likely by sterol ligands. Activated SMO overcomes the negative influence of PKA on the GLI transcription factors, which control gene expression.