Smoothening out the patches

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Science  05 Oct 2018:
Vol. 362, Issue 6410, pp. 26-27
DOI: 10.1126/science.aav1025

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Signaling pathways regulated by the lipidated protein ligand Hedgehog (HH) direct the development of all metazoans through unique molecular mechanisms that remain elusive. More than two decades after their discovery, a series of recently determined structures of two key HH signaling transducers—the transmembrane proteins Patched (PTCH) and Smoothened (SMO)—are now beginning to reveal the signaling events triggered by HH and homologous ligands at the cell membrane. On page 52 of this issue, Qi et al. (1) describe structures derived by cryo–electron microscopy (cryo-EM) that harmonize recent reports (2, 3) of the structure of the HH receptor PTCH, an important tumor suppressor (4). Together with recent crystal structures of the seven-transmembrane-spanning protein SMO (5, 6), they provide important new insight on molecular events in HH signaling and suggest new opportunities for targeting this pathway in cancer and other diseases (4).