PMID: 19561611

 

    Legend: Gene, Sites

Title : Structural insights into hedgehog ligand sequestration by the human hedgehog-interacting protein HHIP

Abstract :

1. Hedgehog (Hh ) morphogens have fundamental roles in development, whereas dysregulation of Hh signaling leads to disease
2. Multiple cell-surface receptors are responsible for transducing and/or regulating Hh signals
3. Among these, the Hedgehog-interacting protein ( Hhip ) is a highly conserved, vertebrate-specific inhibitor of Hh signaling
4. 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 +
5. 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
6. 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
7. This interplay of several metal binding sites suggests a tuneable mechanism for regulation of Hh signaling

Output (sent_index, trigger, protein, sugar, site):

Output(Part-Of) (sent_index, protein, site):

• 4. HHIP, ectodomain
• 5. Ca2, sites--functions

*Output_Site_Fusion* (sent_index, protein, sugar, site):

 

Protein	NCBI ID	SENTENCE INDEX
Hedgehog-interacting protein	64399	3
hedgehog-interacting protein HHIP	64399	0
Hhip	64399	3
HHIP	64399	4,6