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Amy-Doan P

As seen in: PNAS, Caltech
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Articles by Amy-Doan P

The mechanism for ligand activation of the Smoothened G protein–coupled receptor

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By Amy-Doan P
| Caltech
Published July 7, 2026 | Version Published Journal Article Open The Smoothened (SMO) G protein–coupled receptor is a key part of the Hedgehog (Hh) signaling pathway, and it is an oncoprotein that is an important target for understanding cancers such as basal cell carcinoma. However, its mechanism of activation remains unknown. To this end, we investigate here the sequence of G protein and cholesterol (CHL) ligand binding to SMO on the pathway toward activation.
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The mechanism for ligand activation of the Smoothened G protein–coupled receptor

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By Amy-Doan P, Jian Cao, Sheng Liu
| PNAS Verified
A. M. Arensdorf, S. Marada, S. K. Ogden, Smoothened regulation: A tale of two signals. Trends Pharmacol. Sci. 37, 62–72 (2016). G. Cong, X. Zhu, X. R. Chen, H. Chen, W. Chong, Mechanisms and therapeutic potential of the hedgehog signaling pathway in cancer. Cell Death Discov. 11, 40 (2025). A. M. Skoda et al., The role of the hedgehog signaling pathway in cancer: A comprehensive review. Bosn. J. Basic Med. Sci. 18, 8 (2018). J. H. Kong, C. Siebold, R. Rohatgi, Biochemical mechanisms of vertebrate hedgehog signaling.
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Fully activated structure of the sterol-bound Smoothened GPCR-Gi protein complex | Proceedings of the National Academy of Sciences

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By Lainey J. Williamson, Marina Galchenkova, Hannah L. Best, Amy-Doan P
| PNAS Verified
Significance The G protein–coupled receptor Smoothened (SMO) interacts biochemically with Gi proteins and guides cellular differentiation in both embryogenesis and cancer. We report here the fully activated structure of SMO coupled to a Gi protein and bound to sterol ligands, provided by all-atom molecular dynamics simulations.
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