2WG3: Crystal Structure Of The Complex Between Human Hedgehog- Interacting Protein Hip And Desert Hedgehog Without Calcium

Hedgehog (Hh) morphogens have fundamental roles in development, whereas dysregulation of Hh signaling leads to disease. Multiple cell-surface receptors are responsible for transducing and/or regulating Hh signals. Among these, the Hedgehog-interacting protein (Hhip) is a highly conserved, vertebrate-specific inhibitor of Hh signaling. We have solved a series of crystal structures for the human HHIP ectodomain and Desert hedgehog (DHH) in isolation, as well as HHIP in complex with DHH (HHIP-DHH) and Sonic hedgehog (Shh) (HHIP-Shh), with and without Ca2+. The interaction determinants, confirmed by biophysical studies and mutagenesis, reveal previously uncharacterized and distinct functions for the Hh Zn2+ and Ca2+ binding sites--functions that may be common to all vertebrate Hh proteins. Zn2+ makes a key contribution to the Hh-HHIP interface, whereas Ca2+ is likely to prevent electrostatic repulsion between the two proteins, suggesting an important modulatory role. This interplay of several metal binding sites suggests a tuneable mechanism for regulation of Hh signaling.
PDB ID: 2WG3Download
MMDB ID: 74893
PDB Deposition Date: 2009/4/15
Updated in MMDB: 2012/09
Experimental Method:
x-ray diffraction
Resolution: 2.6  Å
Source Organism:
Similar Structures:
Biological Unit for 2WG3: dimeric; determined by author and by software (PISA)
Molecular Components in 2WG3
Label Count Molecule
Proteins (2 molecules)
Desert Hedgehog Protein N-product(Gene symbol: DHH)
Molecule annotation
Hedgehog-interacting Protein(Gene symbol: HHIP)
Molecule annotation
Chemicals (6 molecules)
* Click molecule labels to explore molecular sequence information.

Citing MMDB