Cryo-EM structure of the Hedgehog release protein Dispatched.
- Cannac F Laboratory of Biomolecular Research, Division of Biology and Chemistry, Paul Scherrer Institute, 5232 Villigen, Switzerland.
- Qi C Institute of Biochemistry, ETH-Zürich, 8093 Zürich, Switzerland.
- Falschlunger J Institute of Molecular Life Sciences, University of Zürich, Winterthurerstrasse 190, 8057 Zürich, Switzerland.
- Hausmann G Institute of Molecular Life Sciences, University of Zürich, Winterthurerstrasse 190, 8057 Zürich, Switzerland.
- Basler K Institute of Molecular Life Sciences, University of Zürich, Winterthurerstrasse 190, 8057 Zürich, Switzerland.
- Korkhov VM Laboratory of Biomolecular Research, Division of Biology and Chemistry, Paul Scherrer Institute, 5232 Villigen, Switzerland.
- 2020-06-05
Published in:
- Science advances. - 2020
English
The Hedgehog (Hh) 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, 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-electron microscopy structure of the D. melanogaster Dispatched at 3.2-Å resolution. The ectodomains of Dispatched adopt an open conformation suggestive of a receptor-chaperone role. A three-dimensional 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.
- Language
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- English
- Open access status
- gold
- Identifiers
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- DOI 10.1126/sciadv.aay7928
- PMID 32494603
- Persistent URL
- https://sonar.ch/global/documents/119739
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