Cryo-EM structure of the Hedgehog release protein Dispatched.

Science advances (2020-06-05)
Fabien Cannac, Chao Qi, Julia Falschlunger, George Hausmann, Konrad Basler, Volodymyr M Korkhov
ABSTRACT

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.

MATERIALS
Product Number
Brand
Product Description

Sigma-Aldrich
Insulin from bovine pancreas, powder, BioReagent, suitable for cell culture
Sigma-Aldrich
Shields and Sang M3 Insect Medium, With L-glutamine, without potassium bicarbonate, powder, suitable for insect cell culture