2IBG

Crystal Structure of Hedgehog Bound to the FNIII Domains of Ihog


Experimental Data Snapshot

  • Method: X-RAY DIFFRACTION
  • Resolution: 2.20 Å
  • R-Value Free: 0.246 
  • R-Value Work: 0.198 
  • R-Value Observed: 0.200 

wwPDB Validation   3D Report Full Report


This is version 1.3 of the entry. See complete history


Literature

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

McLellan, J.S.Yao, S.Zheng, X.Geisbrecht, B.V.Ghirlando, R.Beachy, P.A.Leahy, D.J.

(2006) Proc Natl Acad Sci U S A 103: 17208-17213

  • DOI: https://doi.org/10.1073/pnas.0606738103
  • Primary Citation of Related Structures:  
    2IBB, 2IBG, 2IC2

  • 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.


  • Organizational Affiliation

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


Macromolecules
Find similar proteins by:  (by identity cutoff)  |  3D Structure
Entity ID: 1
MoleculeChains Sequence LengthOrganismDetailsImage
CG9211-PA
A, B, C, D
214Drosophila melanogasterMutation(s): 0 
Gene Names: iHogCG9211
UniProt
Find proteins for Q9VM64 (Drosophila melanogaster)
Explore Q9VM64 
Go to UniProtKB:  Q9VM64
Entity Groups  
Sequence Clusters30% Identity50% Identity70% Identity90% Identity95% Identity100% Identity
UniProt GroupQ9VM64
Sequence Annotations
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  • Reference Sequence
Find similar proteins by:  (by identity cutoff)  |  3D Structure
Entity ID: 2
MoleculeChains Sequence LengthOrganismDetailsImage
Protein hedgehog
E, F, G, H
150Drosophila melanogasterMutation(s): 0 
Gene Names: hh
UniProt
Find proteins for Q02936 (Drosophila melanogaster)
Explore Q02936 
Go to UniProtKB:  Q02936
Entity Groups  
Sequence Clusters30% Identity50% Identity70% Identity90% Identity95% Identity100% Identity
UniProt GroupQ02936
Sequence Annotations
Expand
  • Reference Sequence
Small Molecules
Ligands 1 Unique
IDChains Name / Formula / InChI Key2D Diagram3D Interactions
PO4
Query on PO4

Download Ideal Coordinates CCD File 
I [auth A]
J [auth A]
K [auth B]
L [auth B]
M [auth C]
I [auth A],
J [auth A],
K [auth B],
L [auth B],
M [auth C],
N [auth C],
O [auth D],
P [auth E],
Q [auth E],
R [auth E],
S [auth F],
T [auth H]
PHOSPHATE ION
O4 P
NBIIXXVUZAFLBC-UHFFFAOYSA-K
Experimental Data & Validation

Experimental Data

  • Method: X-RAY DIFFRACTION
  • Resolution: 2.20 Å
  • R-Value Free: 0.246 
  • R-Value Work: 0.198 
  • R-Value Observed: 0.200 
  • Space Group: P 1 21 1
Unit Cell:
Length ( Å )Angle ( ˚ )
a = 75.354α = 90
b = 70.003β = 90.18
c = 155.695γ = 90
Software Package:
Software NamePurpose
REFMACrefinement
PDB_EXTRACTdata extraction
HKL-2000data reduction
HKL-2000data scaling
MOLREPphasing

Structure Validation

View Full Validation Report



Entry History 

Deposition Data

Revision History  (Full details and data files)

  • Version 1.0: 2006-10-24
    Type: Initial release
  • Version 1.1: 2008-05-01
    Changes: Version format compliance
  • Version 1.2: 2011-07-13
    Changes: Advisory, Version format compliance
  • Version 1.3: 2023-08-30
    Changes: Data collection, Database references, Derived calculations, Refinement description