ArticleProceedings of the National Academy of Sciences of the United States of America2013
Structural insights into proteoglycan-shaped Hedgehog signaling.
Article in Proceedings of the National Academy of Sciences of the United States of America, 2013. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 51 papers.
What it found
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Who cites it
51 citing papers in PubMed, 104 citations in OpenAlex.
- The Glyco-Code Molecular Template Instructively Guides Skeletal and Neural Development, Tissue Regeneration and Dynamic Repair Responses Following Trauma and Disease.International journal of molecular sciences · 2026Review
- Unconventional Secretion of Angiogenic Sonic Hedgehog-Containing Extra-Large Extracellular Vesicles is Driven by PI3K-Rab18-GDP Signalling.Journal of extracellular biology · 2026Article
- Alcian blue-positive stromal phenotype in basal cell carcinoma is associated with progression on first-line hedgehog inhibitors.The journal of pathology. Clinical research · 2026Article
- Antagonism of the ATP-gated P2X7 receptor inhibits the proliferation of hepatocellular carcinoma cells.Purinergic signalling · 2025Article
- Identification of small molecule antagonists of sonic hedgehog/heparin binding with activity in hedgehog functional assays.Biochimica et biophysica acta. General subjects · 2024Article
- Two-way Dispatched function in Sonic hedgehog shedding and transfer to high-density lipoproteins.eLife · 2024Article
- Review
- Assessing Genetic Algorithm-Based Docking Protocols for Prediction of Heparin Oligosaccharide Binding Geometries onto Proteins.Biomolecules · 2023Article
- The role of glycosaminoglycan modification in Hedgehog regulated tissue morphogenesis.Biochemical Society transactions · 2023Review
- Regulation of morphogen pathways by a Drosophila chondroitin sulfate proteoglycan Windpipe.Journal of cell science · 2023Article
- The dynamic nature of netrin-1 and the structural basis for glycosaminoglycan fragment-induced filament formation.Nature communications · 2023Article
- Hedgehog is relayed through dynamic heparan sulfate interactions to shape its gradient.Nature communications · 2023Article
- Article
- Article
- Structural basis for catalyzed assembly of the Sonic hedgehog-Patched1 signaling complex.Developmental cell · 2022Article
- The extracellular matrix of hematopoietic stem cell niches.Advanced drug delivery reviews · 2022Review
- Roles of Chondroitin Sulfate Proteoglycans as Regulators of Skeletal Development.Frontiers in cell and developmental biology · 2022Review
- Structure, mechanism, and inhibition of Hedgehog acyltransferase.Molecular cell · 2021Article
- Hedgehog-Interacting Protein is a multimodal antagonist of Hedgehog signalling.Nature communications · 2021Article
- Dispatched uses NaNature · 2021Article
Corrections and comments
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Authors and funding
4 authors at 2 institutions in 1 country.
Funding
Abstract
Hedgehog (Hh) morphogens play fundamental roles during embryogenesis and adulthood, in health and disease. Multiple cell surface receptors regulate the Hh signaling pathway. Among these, the glycosaminoglycan (GAG) chains of proteoglycans shape Hh gradients and signal transduction. We have determined crystal structures of Sonic Hh complexes with two GAGs, heparin and chondroitin sulfate. The interaction determinants, confirmed by site-directed mutagenesis and binding studies, reveal a previously not identified Hh site for GAG binding, common to all Hh proteins. The majority of Hh residues forming this GAG-binding site have been previously implicated in developmental diseases. Crystal packing analysis, combined with analytical ultracentrifugation of Sonic Hh-GAG complexes, suggests a potential mechanism for GAG-dependent Hh multimerization. Taken together, these results provide a direct mechanistic explanation of the observed correlation between disease and impaired Hh gradient formation. Moreover, GAG binding partially overlaps with the site of Hh interactions with an array of protein partners including Patched, hedgehog interacting protein, and the interference hedgehog protein family, suggesting a unique mechanism of Hh signaling modulation.
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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.