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| | <StructureSection load='2wfx' size='340' side='right'caption='[[2wfx]], [[Resolution|resolution]] 3.20Å' scene=''> | | <StructureSection load='2wfx' size='340' side='right'caption='[[2wfx]], [[Resolution|resolution]] 3.20Å' scene=''> |
| | == Structural highlights == | | == Structural highlights == |
| - | <table><tr><td colspan='2'>[[2wfx]] is a 2 chain structure with sequence from [https://en.wikipedia.org/wiki/Human Human] and [https://en.wikipedia.org/wiki/Lk3_transgenic_mice Lk3 transgenic mice]. Full crystallographic information is available from [http://oca.weizmann.ac.il/oca-bin/ocashort?id=2WFX OCA]. For a <b>guided tour on the structure components</b> use [https://proteopedia.org/fgij/fg.htm?mol=2WFX FirstGlance]. <br> | + | <table><tr><td colspan='2'>[[2wfx]] is a 2 chain structure with sequence from [https://en.wikipedia.org/wiki/Homo_sapiens Homo sapiens] and [https://en.wikipedia.org/wiki/Mus_musculus Mus musculus]. Full crystallographic information is available from [http://oca.weizmann.ac.il/oca-bin/ocashort?id=2WFX OCA]. For a <b>guided tour on the structure components</b> use [https://proteopedia.org/fgij/fg.htm?mol=2WFX FirstGlance]. <br> |
| - | </td></tr><tr id='ligand'><td class="sblockLbl"><b>[[Ligand|Ligands:]]</b></td><td class="sblockDat" id="ligandDat"><scene name='pdbligand=CA:CALCIUM+ION'>CA</scene>, <scene name='pdbligand=NA:SODIUM+ION'>NA</scene>, <scene name='pdbligand=ZN:ZINC+ION'>ZN</scene></td></tr> | + | </td></tr><tr id='method'><td class="sblockLbl"><b>[[Empirical_models|Method:]]</b></td><td class="sblockDat" id="methodDat">X-ray diffraction, [[Resolution|Resolution]] 3.2Å</td></tr> |
| - | <tr id='related'><td class="sblockLbl"><b>[[Related_structure|Related:]]</b></td><td class="sblockDat"><div style='overflow: auto; max-height: 3em;'>[[2wft|2wft]], [[2wg4|2wg4]], [[1vhh|1vhh]], [[2wg3|2wg3]], [[2wgr|2wgr]], [[2wgq|2wgq]]</div></td></tr>
| + | <tr id='ligand'><td class="sblockLbl"><b>[[Ligand|Ligands:]]</b></td><td class="sblockDat" id="ligandDat"><scene name='pdbligand=CA:CALCIUM+ION'>CA</scene>, <scene name='pdbligand=NA:SODIUM+ION'>NA</scene>, <scene name='pdbligand=ZN:ZINC+ION'>ZN</scene></td></tr> |
| | <tr id='resources'><td class="sblockLbl"><b>Resources:</b></td><td class="sblockDat"><span class='plainlinks'>[https://proteopedia.org/fgij/fg.htm?mol=2wfx FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=2wfx OCA], [https://pdbe.org/2wfx PDBe], [https://www.rcsb.org/pdb/explore.do?structureId=2wfx RCSB], [https://www.ebi.ac.uk/pdbsum/2wfx PDBsum], [https://prosat.h-its.org/prosat/prosatexe?pdbcode=2wfx ProSAT]</span></td></tr> | | <tr id='resources'><td class="sblockLbl"><b>Resources:</b></td><td class="sblockDat"><span class='plainlinks'>[https://proteopedia.org/fgij/fg.htm?mol=2wfx FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=2wfx OCA], [https://pdbe.org/2wfx PDBe], [https://www.rcsb.org/pdb/explore.do?structureId=2wfx RCSB], [https://www.ebi.ac.uk/pdbsum/2wfx PDBsum], [https://prosat.h-its.org/prosat/prosatexe?pdbcode=2wfx ProSAT]</span></td></tr> |
| | </table> | | </table> |
| | == Function == | | == Function == |
| - | [[https://www.uniprot.org/uniprot/SHH_MOUSE SHH_MOUSE]] Binds to the patched (PTC) receptor, which functions in association with smoothened (SMO), to activate the transcription of target genes. In the absence of SHH, PTC represses the constitutive signaling activity of SMO. Also regulates another target, the gli oncogene. Intercellular signal essential for a variety of patterning events during development: signal produced by the notochord that induces ventral cell fate in the neural tube and somites, and the polarizing signal for patterning of the anterior-posterior axis of the developing limb bud. Displays both floor plate- and motor neuron-inducing activity. The threshold concentration of N-product required for motor neuron induction is 5-fold lower than that required for floor plate induction (By similarity).<ref>PMID:7736596</ref> [[https://www.uniprot.org/uniprot/HHIP_HUMAN HHIP_HUMAN]] Modulates hedgehog signaling in several cell types including brain and lung through direct interaction with members of the hedgehog family.<ref>PMID:11472839</ref> <ref>PMID:19561609</ref>
| + | [https://www.uniprot.org/uniprot/SHH_MOUSE SHH_MOUSE] Binds to the patched (PTC) receptor, which functions in association with smoothened (SMO), to activate the transcription of target genes. In the absence of SHH, PTC represses the constitutive signaling activity of SMO. Also regulates another target, the gli oncogene. Intercellular signal essential for a variety of patterning events during development: signal produced by the notochord that induces ventral cell fate in the neural tube and somites, and the polarizing signal for patterning of the anterior-posterior axis of the developing limb bud. Displays both floor plate- and motor neuron-inducing activity. The threshold concentration of N-product required for motor neuron induction is 5-fold lower than that required for floor plate induction (By similarity).<ref>PMID:7736596</ref> |
| | == Evolutionary Conservation == | | == Evolutionary Conservation == |
| | [[Image:Consurf_key_small.gif|200px|right]] | | [[Image:Consurf_key_small.gif|200px|right]] |
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| | | | |
| | ==See Also== | | ==See Also== |
| - | *[[Sonic Hedgehog|Sonic Hedgehog]] | + | *[[Sonic hedgehog 3D structures|Sonic hedgehog 3D structures]] |
| | == References == | | == References == |
| | <references/> | | <references/> |
| | __TOC__ | | __TOC__ |
| | </StructureSection> | | </StructureSection> |
| - | [[Category: Human]] | + | [[Category: Homo sapiens]] |
| | [[Category: Large Structures]] | | [[Category: Large Structures]] |
| - | [[Category: Lk3 transgenic mice]] | + | [[Category: Mus musculus]] |
| - | [[Category: Aricescu, A R]] | + | [[Category: Aricescu AR]] |
| - | [[Category: Bishop, B]] | + | [[Category: Bishop B]] |
| - | [[Category: Callaghan, C A.O]]
| + | [[Category: Harlos K]] |
| - | [[Category: Harlos, K]] | + | [[Category: Jones EY]] |
| - | [[Category: Jones, E Y]] | + | [[Category: O'Callaghan CA]] |
| - | [[Category: Siebold, C]] | + | [[Category: Siebold C]] |
| - | [[Category: Autocatalytic cleavage]] | + | |
| - | [[Category: Cell membrane]]
| + | |
| - | [[Category: Development]]
| + | |
| - | [[Category: Developmental protein]]
| + | |
| - | [[Category: Disulfide bond]]
| + | |
| - | [[Category: Egf-like domain]]
| + | |
| - | [[Category: Glycoprotein]]
| + | |
| - | [[Category: Hedgehog signaling]]
| + | |
| - | [[Category: Hydrolase]]
| + | |
| - | [[Category: Lipoprotein]]
| + | |
| - | [[Category: Membrane]]
| + | |
| - | [[Category: Palmitate]]
| + | |
| - | [[Category: Protease]]
| + | |
| - | [[Category: Secreted]]
| + | |
| - | [[Category: Signal transduction]]
| + | |
| - | [[Category: Signaling protein]]
| + | |
| Structural highlights
Function
SHH_MOUSE Binds to the patched (PTC) receptor, which functions in association with smoothened (SMO), to activate the transcription of target genes. In the absence of SHH, PTC represses the constitutive signaling activity of SMO. Also regulates another target, the gli oncogene. Intercellular signal essential for a variety of patterning events during development: signal produced by the notochord that induces ventral cell fate in the neural tube and somites, and the polarizing signal for patterning of the anterior-posterior axis of the developing limb bud. Displays both floor plate- and motor neuron-inducing activity. The threshold concentration of N-product required for motor neuron induction is 5-fold lower than that required for floor plate induction (By similarity).[1]
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[2]
From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine.
See Also
References
- ↑ Roelink H, Porter JA, Chiang C, Tanabe Y, Chang DT, Beachy PA, Jessell TM. Floor plate and motor neuron induction by different concentrations of the amino-terminal cleavage product of sonic hedgehog autoproteolysis. Cell. 1995 May 5;81(3):445-55. PMID:7736596
- ↑ Bishop B, Aricescu AR, Harlos K, O'Callaghan CA, Jones EY, Siebold C. Structural insights into hedgehog ligand sequestration by the human hedgehog-interacting protein HHIP. Nat Struct Mol Biol. 2009 Jul;16(7):698-703. Epub 2009 Jun 28. PMID:19561611 doi:10.1038/nsmb.1607
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