2wft

Crystal structure of the human HIP ectodomain

spinqualitylabelsall models 2wft, resolution 2.80Å Show:Asymmetric Unit Biological Assembly Drag the structure with the mouse to rotate   Export Animated Image   Print3D Structural highlights 2wft is a 2 chain structure with sequence from Human. Full crystallographic information is available from OCA. For a guided tour on the structure components use FirstGlance. Ligands: CL, NA Related: 2wfx, 2wg4, 2wg3, 2wfq, 2wfr Resources: FirstGlance, OCA, PDBe, RCSB, PDBsum, ProSAT Function [HHIP_HUMAN] Modulates hedgehog signaling in several cell types including brain and lung through direct interaction with members of the hedgehog family. Evolutionary Conservation Check, as determined by ConSurfDB. You may read the explanation of the method and the full data available from ConSurf. Publication Abstract from PubMed 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. Structural insights into hedgehog ligand sequestration by the human hedgehog-interacting protein HHIP.,Bishop B, Aricescu AR, Harlos K, O'Callaghan CA, Jones EY, Siebold C Nat Struct Mol Biol. 2009 Jul;16(7):698-703. Epub 2009 Jun 28. PMID:19561611 From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine.

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