2IBG

Crystal Structure of Hedgehog Bound to the FNIII Domains of Ihog

Summary for 2IBG

• Entry DOI: 10.2210/pdb2ibg/pdb
• Related: 2IBB
• Descriptor: CG9211-PA, Protein hedgehog, PHOSPHATE ION, ... (4 entities in total)
• Functional Keywords: ihog, hedgehog, fibronectin type iii, protein binding
• Biological source: Drosophila melanogaster (fruit fly); More
• Cellular location: Membrane; Single-pass type I membrane protein (Potential): Q9VM64; Nucleus. Protein hedgehog N-product: Cell membrane; Lipid-anchor; Extracellular side. Protein hedgehog C-product: Secreted, extracellular space: Q02936
• Total number of polymer chains: 8
• Total formula weight: 167386.77

Authors

McLellan, J.S.,Leahy, D.J. (deposition date: 2006-09-11, release date: 2006-10-24, Last modification date: 2023-08-30)

Primary citation

McLellan, J.S.,Yao, S.,Zheng, X.,Geisbrecht, B.V.,Ghirlando, R.,Beachy, P.A.,Leahy, D.J.
Structure of a heparin-dependent complex of Hedgehog and Ihog.
Proc.Natl.Acad.Sci.Usa, 103:17208-17213, 2006

PubMed 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.

PubMed: 17077139
DOI: 10.1073/pnas.0606738103

Experimental method

X-RAY DIFFRACTION (2.2 Å)