RT Journal Article SR Electronic T1 Cryo-EM structure of the Hedgehog release protein Dispatched JF bioRxiv FD Cold Spring Harbor Laboratory SP 707513 DO 10.1101/707513 A1 Fabien Cannac A1 Chao Qi A1 Julia Falschlunger A1 George Hausmann A1 Konrad Basler A1 Volodymyr M. Korkhov YR 2019 UL http://biorxiv.org/content/early/2019/07/18/707513.abstract AB The Hedgehog signaling pathway controls embryonic development and adult tissue homeostasis in multicellular organisms. In Drosophila melanogaster, the pathway is primed by secretion of a dually lipid-modified morphogen, Hedgehog (Hh), a process dependent on a membrane-integral protein Dispatched. Although Dispatched is a critical component of the pathway, the structural basis of its activity has so far not been described. Here, we describe a cryo-EM structure of the Drosophila melanogaster Dispatched at 3.2 Å resolution. The ectodomains of Dispatched adopt an open conformation suggestive of a receptor-chaperone role. A 3D reconstruction of Dispatched bound to Hh confirms the ability of Dispatched to bind Hh but using a unique mode distinct from those previously observed in structures of Hh complexes. The structure may represent the state of the complex that precedes shedding of Hh from the surface of the morphogen-releasing cell.