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< | ==Crystal structure of Hedgehog-interacting protein (HHIP) and Sonic hedgehog (SHH) complex== | ||
<StructureSection load='3ho5' size='340' side='right'caption='[[3ho5]], [[Resolution|resolution]] 3.01Å' scene=''> | |||
You may | == Structural highlights == | ||
<table><tr><td colspan='2'>[[3ho5]] is a 3 chain structure with sequence from [https://en.wikipedia.org/wiki/Homo_sapiens Homo sapiens]. Full crystallographic information is available from [http://oca.weizmann.ac.il/oca-bin/ocashort?id=3HO5 OCA]. For a <b>guided tour on the structure components</b> use [https://proteopedia.org/fgij/fg.htm?mol=3HO5 FirstGlance]. <br> | |||
</td></tr><tr id='method'><td class="sblockLbl"><b>[[Empirical_models|Method:]]</b></td><td class="sblockDat" id="methodDat">X-ray diffraction, [[Resolution|Resolution]] 3.01Å</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=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=3ho5 FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=3ho5 OCA], [https://pdbe.org/3ho5 PDBe], [https://www.rcsb.org/pdb/explore.do?structureId=3ho5 RCSB], [https://www.ebi.ac.uk/pdbsum/3ho5 PDBsum], [https://prosat.h-its.org/prosat/prosatexe?pdbcode=3ho5 ProSAT]</span></td></tr> | |||
</table> | |||
== Function == | |||
[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> | |||
== Evolutionary Conservation == | |||
[[Image:Consurf_key_small.gif|200px|right]] | |||
Check<jmol> | |||
<jmolCheckbox> | |||
<scriptWhenChecked>; select protein; define ~consurf_to_do selected; consurf_initial_scene = true; script "/wiki/ConSurf/ho/3ho5_consurf.spt"</scriptWhenChecked> | |||
<scriptWhenUnchecked>script /wiki/extensions/Proteopedia/spt/initialview03.spt</scriptWhenUnchecked> | |||
<text>to colour the structure by Evolutionary Conservation</text> | |||
</jmolCheckbox> | |||
</jmol>, as determined by [http://consurfdb.tau.ac.il/ ConSurfDB]. You may read the [[Conservation%2C_Evolutionary|explanation]] of the method and the full data available from [http://bental.tau.ac.il/new_ConSurfDB/main_output.php?pdb_ID=3ho5 ConSurf]. | |||
<div style="clear:both"></div> | |||
<div style="background-color:#fffaf0;"> | |||
== Publication Abstract from PubMed == | |||
Hedgehog (Hh) signaling is crucial for many aspects of embryonic development, whereas dysregulation of this pathway is associated with several types of cancer. Hedgehog-interacting protein (Hhip) is a surface receptor antagonist that is equipotent against all three mammalian Hh homologs. The crystal structures of human HHIP alone and bound to Sonic hedgehog (SHH) now reveal that HHIP is comprised of two EGF domains and a six-bladed beta-propeller domain. In the complex structure, a critical loop from HHIP binds the pseudo active site groove of SHH and directly coordinates its Zn2+ cation. Notably, sequence comparisons of this SHH binding loop with the Hh receptor Patched (Ptc1) ectodomains and HHIP- and PTC1-peptide binding studies suggest a 'patch for Patched' at the Shh pseudo active site; thus, we propose a role for Hhip as a structural decoy receptor for vertebrate Hh. | |||
The structure of SHH in complex with HHIP reveals a recognition role for the Shh pseudo active site in signaling.,Bosanac I, Maun HR, Scales SJ, Wen X, Lingel A, Bazan JF, de Sauvage FJ, Hymowitz SG, Lazarus RA Nat Struct Mol Biol. 2009 Jul;16(7):691-7. Epub 2009 Jun 28. PMID:19561609<ref>PMID:19561609</ref> | |||
From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine.<br> | |||
</div> | |||
<div class="pdbe-citations 3ho5" style="background-color:#fffaf0;"></div> | |||
==See Also== | |||
*[[Sonic hedgehog 3D structures|Sonic hedgehog 3D structures]] | |||
== References == | |||
<references/> | |||
__TOC__ | |||
</StructureSection> | |||
== | |||
== | |||
< | |||
[[Category: Homo sapiens]] | [[Category: Homo sapiens]] | ||
[[Category: | [[Category: Large Structures]] | ||
[[Category: | [[Category: Bosanac I]] | ||
[[Category: | [[Category: Hymowitz SG]] | ||
Latest revision as of 08:52, 17 October 2024
Crystal structure of Hedgehog-interacting protein (HHIP) and Sonic hedgehog (SHH) complexCrystal structure of Hedgehog-interacting protein (HHIP) and Sonic hedgehog (SHH) complex
Structural highlights
FunctionHHIP_HUMAN Modulates hedgehog signaling in several cell types including brain and lung through direct interaction with members of the hedgehog family.[1] [2] 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 PubMedHedgehog (Hh) signaling is crucial for many aspects of embryonic development, whereas dysregulation of this pathway is associated with several types of cancer. Hedgehog-interacting protein (Hhip) is a surface receptor antagonist that is equipotent against all three mammalian Hh homologs. The crystal structures of human HHIP alone and bound to Sonic hedgehog (SHH) now reveal that HHIP is comprised of two EGF domains and a six-bladed beta-propeller domain. In the complex structure, a critical loop from HHIP binds the pseudo active site groove of SHH and directly coordinates its Zn2+ cation. Notably, sequence comparisons of this SHH binding loop with the Hh receptor Patched (Ptc1) ectodomains and HHIP- and PTC1-peptide binding studies suggest a 'patch for Patched' at the Shh pseudo active site; thus, we propose a role for Hhip as a structural decoy receptor for vertebrate Hh. The structure of SHH in complex with HHIP reveals a recognition role for the Shh pseudo active site in signaling.,Bosanac I, Maun HR, Scales SJ, Wen X, Lingel A, Bazan JF, de Sauvage FJ, Hymowitz SG, Lazarus RA Nat Struct Mol Biol. 2009 Jul;16(7):691-7. Epub 2009 Jun 28. PMID:19561609[3] From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine. See AlsoReferences
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