Hedgehog pathway activation through nanobody-mediated conformational blockade of the Patched sterol conduit

We recently published “Hedgehog pathway activation through nanobody-mediated conformational blockade of the Patched sterol conduit” in Proceedings of the National Academy of Sciences.

Precise manipulation of Hedgehog pathway activity holds great value for biological research and clinical applications, but pathway agonists amenable to engineering have been lacking. We selected a nanobody that potentially targets the conformational changes of the Hedgehog receptor Patched1 and demonstrated that this nanobody potently activates the pathway in vivo. This nanobody can serve as the basis for mechanistic studies of Hedgehog pathway activation and for potential therapeutic applications. Our method may further apply to the investigation of other related transporters in the Resistance-Nodulation-Division superfamily.