2WG4
Crystal structure of the complex between human hedgehog-interacting protein HIP and sonic hedgehog without calcium
Summary for 2WG4
| Entry DOI | 10.2210/pdb2wg4/pdb |
| Related | 1VHH 2WFQ 2WFR 2WFT 2WFX 2WG3 |
| Descriptor | SONIC HEDGEHOG PROTEIN N-PRODUCT, HEDGEHOG-INTERACTING PROTEIN, ZINC ION, ... (4 entities in total) |
| Functional Keywords | autocatalytic cleavage, protease, membrane, secreted, palmitate, hydrolase, signal transduction, developmental protein, signaling protein, lipoprotein, development, glycoprotein, cell membrane, disulfide bond, egf-like domain, hedgehog signaling |
| Biological source | MUS MUSCULUS (MOUSE) More |
| Cellular location | Sonic hedgehog protein N-product: Cell membrane ; Lipid-anchor : Q62226 Cell membrane ; Peripheral membrane protein . Isoform 2: Cytoplasm : Q96QV1 |
| Total number of polymer chains | 2 |
| Total formula weight | 68736.90 |
| Authors | Bishop, B.,Aricescu, A.R.,Harlos, K.,O'Callaghan, C.A.,Jones, E.Y.,Siebold, C. (deposition date: 2009-04-15, release date: 2009-06-30, Last modification date: 2024-11-06) |
| Primary citation | Bishop, B.,Aricescu, A.R.,Harlos, K.,O'Callaghan, C.A.,Jones, E.Y.,Siebold, C. Structural Insights Into Hedgehog Ligand Sequestration by the Human Hedgehog-Interacting Protein Hip Nat.Struct.Mol.Biol., 16:698-, 2009 Cited by PubMed Abstract: 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. PubMed: 19561611DOI: 10.1038/NSMB.1607 PDB entries with the same primary citation |
| Experimental method | X-RAY DIFFRACTION (3.15 Å) |
Structure validation
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