ArticleNature chemical biology2019
The morphogen Sonic hedgehog inhibits its receptor Patched by a pincer grasp mechanism.
Article in Nature chemical biology, 2019. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 44 papers.
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Who cites it
44 citing papers in PubMed, 75 citations in OpenAlex.
- The SLC-ome of membrane transport: from molecular discovery to physiology and clinical applications.Physiological reviews · 2026Review
- Mechanistic trade-offs between local and long-range signaling activity in natural and synthetic morphogens.Science advances · 2026Article
- Research progress on the Sonic Hedgehog signaling pathway in the central nervous system: Novel insights.Neural regeneration research · 2026Article
- Direct or indirect: the crucial role of N-palmitate in hedgehog signaling.Biochemical Society transactions · 2026Review
- In vitro reconstitution of vertebrate Sonic Hedgehog protein cholesterolysis.bioRxiv : the preprint server for biology · 2026Article
- Article
- Proximity based proteomics reveals Git1 as a regulator of Smoothened signaling.bioRxiv : the preprint server for biology · 2025Article
- Identification of small molecule antagonists of sonic hedgehog/heparin binding with activity in hedgehog functional assays.Biochimica et biophysica acta. General subjects · 2024Article
- Diffusion barriers imposed by tissue topology shape Hedgehog morphogen gradients.Proceedings of the National Academy of Sciences of the United States of America · 2024Article
- Numb positively regulates Hedgehog signaling at the ciliary pocket.Nature communications · 2024Article
- Review
- Imperatorin Suppresses Aberrant Hedgehog Pathway and Overcomes Smoothened Antagonist Resistance via STAT3 Inhibition.Drug design, development and therapy · 2024Article
- The energetics and ion coupling of cholesterol transport through Patched1.Science advances · 2023Article
- HIB/SPOP inhibits Ci/Gli-mediated tumorigenesis by modulating the RNA Polymerase II components stabilities.iScience · 2023Article
- The Inseparable Relationship Between Cholesterol and Hedgehog Signaling.Annual review of biochemistry · 2023Review
- The Energetics and Ion Coupling of Cholesterol Transport Through Patched1.bioRxiv : the preprint server for biology · 2023Article
- The emerging roles of Hedgehog signaling in tumor immune microenvironment.Frontiers in oncology · 2023Review
- New insight into the role of PTCH1 protein in serous ovarian carcinomas.International journal of oncology · 2022Article
- Hedgehog signaling mechanism and role in cancer.Seminars in cancer biology · 2022Review
- CNPY4 inhibits the Hedgehog pathway by modulating membrane sterol lipids.Nature communications · 2022Article
Corrections and comments
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Authors and funding
17 authors at 7 institutions in 3 countries.
Funding
Abstract
Hedgehog (HH) ligands, classical morphogens that pattern embryonic tissues in all animals, are covalently coupled to two lipids-a palmitoyl group at the N terminus and a cholesteroyl group at the C terminus. While the palmitoyl group binds and inactivates Patched 1 (PTCH1), the main receptor for HH ligands, the function of the cholesterol modification has remained mysterious. Using structural and biochemical studies, along with reassessment of previous cryo-electron microscopy structures, we find that the C-terminal cholesterol attached to Sonic hedgehog (Shh) binds the first extracellular domain of PTCH1 and promotes its inactivation, thus triggering HH signaling. Molecular dynamics simulations show that this interaction leads to the closure of a tunnel through PTCH1 that serves as the putative conduit for sterol transport. Thus, Shh inactivates PTCH1 by grasping its extracellular domain with two lipidic pincers, the N-terminal palmitate and the C-terminal cholesterol, which are both inserted into the PTCH1 protein core.
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Registered trials
Read under generation 80e0d062 · epoch 390. Bibliography from PubMed, PubMed Central and OpenAlex; grants from NIH RePORTER; trial links from ClinicalTrials.gov; estimates, votes and beliefs from the OpenQuestion graph.