ArticleeLife2013
Structure and function of the Smoothened extracellular domain in vertebrate Hedgehog signaling.
Article in eLife, 2013. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 96 papers.
What it found
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The abstract states no effect estimate the extractor could read, or names no intervention and outcome on the map, so this paper lights no cell and moves no belief. It is still indexed, cited and linked below.
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Who cites it
96 citing papers in PubMed, 164 citations in OpenAlex.
- Protein Frustration Reveals Orthosteric and Allosteric Active Sites in GPCR:G Protein Complexes.Journal of chemical information and modeling · 2026Article
- Receptor allostery promotes context-specific Sonic Hedgehog signaling during embryonic development.Nature communications · 2026Article
- Structural mechanism for noncanonical GPCR signaling in the Hedgehog pathway.Nature structural & molecular biology · 2026Article
- Article
- Cortisol regulates neonatal lung development via Smoothened.Respiratory research · 2025Article
- Cyclopamine modulates smoothened receptor activity in a binding position dependent manner.Communications biology · 2024Article
- Structure and function of the ROR2 cysteine-rich domain in vertebrate noncanonical WNT5A signaling.eLife · 2024Article
- Binding Position Dependent Modulation of Smoothened Activity by Cyclopamine.bioRxiv : the preprint server for biology · 2024Article
- Fully activated structure of the sterol-bound Smoothened GPCR-Gi protein complex.Proceedings of the National Academy of Sciences of the United States of America · 2023Article
- Phosphatidic acid binding to Patched contributes to the inhibition of Smoothened and Hedgehog signaling inScience signaling · 2023Article
- Cellular and molecular mechanisms of Hedgehog signalling.Nature reviews. Molecular cell biology · 2023Review
- The Inseparable Relationship Between Cholesterol and Hedgehog Signaling.Annual review of biochemistry · 2023Review
- Activation mechanism of the human Smoothened receptor.Biophysical journal · 2023Article
- The emerging roles of Hedgehog signaling in tumor immune microenvironment.Frontiers in oncology · 2023Review
- Aberrant Cholesterol Metabolism and Wnt/β-Catenin Signaling Coalesce via Frizzled5 in Supporting Cancer Growth.Advanced science (Weinheim, Baden-Wurttemberg, Germany) · 2022Article
- Patched 1 regulates Smoothened by controlling sterol binding to its extracellular cysteine-rich domain.Science advances · 2022Article
- Hedgehog signaling and its molecular perspective with cholesterol: a comprehensive review.Cellular and molecular life sciences : CMLS · 2022Review
- TMED2 binding restricts SMO to the ER and Golgi compartments.PLoS biology · 2022Article
- Identification of unusual oxysterols biosynthesised in human pregnancy by charge-tagging and liquid chromatography - mass spectrometry.Frontiers in endocrinology · 2022Article
- The Intimate Connection Between Lipids and Hedgehog Signaling.Frontiers in cell and developmental biology · 2022Review
36 more citing papers are in PubMed but not listed here.
Corrections and comments
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Authors and funding
10 authors at 6 institutions in 3 countries.
Funding
Abstract
The Hedgehog (Hh) signal is transduced across the membrane by the heptahelical protein Smoothened (Smo), a developmental regulator, oncoprotein and drug target in oncology. We present the 2.3 Å crystal structure of the extracellular cysteine rich domain (CRD) of vertebrate Smo and show that it binds to oxysterols, endogenous lipids that activate Hh signaling. The oxysterol-binding groove in the Smo CRD is analogous to that used by Frizzled 8 to bind to the palmitoleyl group of Wnt ligands and to similar pockets used by other Frizzled-like CRDs to bind hydrophobic ligands. The CRD is required for signaling in response to native Hh ligands, showing that it is an important regulatory module for Smo activation. Indeed, targeting of the Smo CRD by oxysterol-inspired small molecules can block signaling by all known classes of Hh activators and by clinically relevant Smo mutants. DOI:http://dx.doi.org/10.7554/eLife.01340.001.
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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.