Structures of human Patched and its complex with native palmitoylated sonic hedgehog.

ABSTRACT: Hedgehog (HH) signalling governs embryogenesis and adult tissue homeostasis in mammals and other multicellular organisms^1-3. Whereas deficient HH signalling leads to birth defects, unrestrained HH signalling is implicated in human cancers^2,4-6. N-terminally palmitoylated HH releases the repression of Patched to the oncoprotein smoothened (SMO); however, the mechanism by which HH recognizes Patched is unclear. Here we report cryo-electron microscopy structures of human patched 1 (PTCH1) alone and in complex with the N-terminal domain of 'native' sonic hedgehog (native SHH-N has both a C-terminal cholesterol and an N-terminal fatty-acid modification), at resolutions of 3.5 Å and 3.8 Å, respectively. The structure of PTCH1 has internal two-fold pseudosymmetry in the tran

SUBMITTER: Qi X 

PROVIDER: S-EPMC6341490 | biostudies-literature | 2018 Aug

REPOSITORIES: biostudies-literature