My NCBISign In

Display Settings:

Format

Send to:

Choose Destination
    Proc Natl Acad Sci U S A. 2006 Nov 14;103(46):17208-13. Epub 2006 Oct 31.

    Structure of a heparin-dependent complex of Hedgehog and Ihog.

    McLellan JS, Yao S, Zheng X, Geisbrecht BV, Ghirlando R, Beachy PA, Leahy DJ.

    Source

    Department of Biophysics and Biophysical Chemistry, Johns Hopkins University School of Medicine, Baltimore, MD 21205, USA.

    Abstract

    Hedgehog (Hh) signaling molecules mediate key tissue-patterning events during animal development, and inappropriate activation of Hh signaling in adults has been associated with human cancers. Recently, a conserved family of type I integral membrane proteins required for normal response to the Hh signal was discovered. One member of this family, Ihog (interference hedgehog), functions upstream or at the level of Patched (Ptc), but how Ihog participates in Hh signaling remains unclear. Here, we show that heparin binding induces Ihog dimerization and is required to mediate high-affinity interactions between Ihog and Hh. We also present crystal structures of a Hh-binding fragment of Ihog, both alone and complexed with Hh. Heparin is not well ordered in these structures, but a basic cleft in the first FNIII domain of Ihog (IhogFn1) is shown by mutagenesis to mediate heparin binding. These results establish that Hh directly binds Ihog and provide the first demonstration of a specific role for heparin in Hh responsiveness.

    Comment in

    PMID:
    17077139
    [PubMed - indexed for MEDLINE]
    PMCID:
    PMC1859911
    Free PMC Article

    Images from this publication.See all images (5) Free text

    Fig. 1.
    Fig. 3.
    Fig. 5.
    Fig. 2.
    Fig. 4.

    Publication Types, MeSH Terms, Substances, Secondary Source ID

    Publication Types

    MeSH Terms

    Substances

    Secondary Source ID

    LinkOut - more resources

    Full Text Sources

    Other Literature Sources

    Medical

    Molecular Biology Databases

    Libraries

      Supplemental Content

      Icon for HighWire Press Icon for PubMed Central Icon for F1000

      Save items

      loading

      Related citations in PubMed

      See reviews... See all...

      Cited by 20 PubMed Central articles

      See all...

      Structures reported by this article

      See all 3 structures...

      Related information

      • Related Citations
        Calculated set of PubMed citations closely related to the selected article(s) retrieved using a word weight algorithm. Related articles are displayed in ranked order from most to least relevant, with the “linked from” citation displayed first.
      • BioSystems
        Pathways and biological systems (BioSystems) that cite the current articles. Citations are from the BioSystems source databases (KEGG and BioCyc).
      • Gene
        Gene records that cite the current articles. Citations in Gene are added manually by NCBI or imported from outside public resources.
      • Gene (GeneRIF)
        Gene records that have the current articles as Reference into Function citations (GeneRIFs). NLM staff reviewing the literature while indexing MEDLINE add GeneRIFs manually.
      • HomoloGene
        HomoloGene clusters of homologous genes and sequences that cite the current articles. These are references on the Gene and sequence records in the HomoloGene entry.
      • Nucleotide (RefSeq)
        NCBI nucleotide Reference Sequences (RefSeqs) that are cited in the current articles, included in the corresponding Gene Reference into Function, or that include the PubMed articles as references.
      • Nucleotide (Weighted)
        Nucleotide records associated with the current articles through the Gene database. These are the related sequences on the Gene record that are added manually by NCBI.
      • Protein (RefSeq)
        NCBI protein Reference Sequences (RefSeqs) that are cited in the current articles, included in the corresponding Gene Reference into Function, or that include the PubMed articles as references.
      • Protein (Weighted)
        Protein records associated with the current articles through related Gene database records. These are the related sequences on the Gene record that are added manually by NCBI.
      • References for this PMC Article
        Citation referenced in PubMed article. Only valid for PubMed citations that are also in PMC.
      • Substance (MeSH Keyword)
        PubChem chemical substance (submitted) records that are classified under the same Medical Subject Headings (MeSH) controlled vocabulary as the current articles.
      • Taxonomy via GenBank
        Taxonomy records associated with the current articles through taxonomic information on related molecular database records (Nucleotide, Protein, Gene, SNP, Structure).
      • UniGene
        UniGene clusters of expressed sequences that are associated with the current articles through references on the clustered sequence records and related Gene records.
      • Protein
        Protein translation features of primary database (GenBank) nucleotide records reported in the current articles as well as Reference Sequences (RefSeqs) that include the articles as references.
      • Structure
        Three-dimensional structure records in the NCBI Structure database for data reported in the current articles.
      • GEO Profiles
        Gene Expression Omnibus (GEO) Profiles of molecular abundance data. The current articles are references on the Gene record associated with the GEO profile.
      • Free in PMC
        Free full text articles in PMC
      • Cited in PMC
        Full-text articles in the PubMed Central Database that cite the current articles.

      Recent activity

      Clear Turn Off Turn On

      Your browsing activity is empty.

      Activity recording is turned off.

      Turn recording back on

      See more...
      You are here: NCBI > Literature > PubMed
      Write to the Help Desk