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3d1m

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Revision as of 08:40, 25 October 2017

Crystal Structure of Sonic Hedgehog Bound to the third FNIII domain of CDO

Structural highlights

3d1m is a 4 chain structure with sequence from Human and Lk3 transgenic mice. Full crystallographic information is available from OCA. For a guided tour on the structure components use FirstGlance.
Ligands:	,
Gene:	Shh, Hhg1 (LK3 transgenic mice), CDON, CDO (HUMAN)
Resources:	FirstGlance, OCA, PDBe, RCSB, PDBsum, ProSAT

Disease

[CDON_HUMAN] Defects in CDON are the cause of holoprosencephaly type 11 (HPE11) [MIM:614226]. HPE11 is a structural anomaly of the brain, in which the developing forebrain fails to correctly separate into right and left hemispheres. Holoprosencephaly is genetically heterogeneous and associated with several distinct facies and phenotypic variability.

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] [CDON_HUMAN] Component of a cell-surface receptor complex that mediates cell-cell interactions between muscle precursor cells. Promotes differentiation of myogenic cells (By similarity).

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) proteins specify tissue pattern in metazoan embryos by forming gradients that emanate from discrete sites of expression and elicit concentration-dependent cellular differentiation or proliferation responses. Cellular responses to Hh and the movement of Hh through tissues are both precisely regulated, and abnormal Hh signalling has been implicated in human birth defects and cancer. Hh signalling is mediated by its amino-terminal domain (HhN), which is dually lipidated and secreted as part of a multivalent lipoprotein particle. Reception of the HhN signal is modulated by several cell-surface proteins on responding cells, including Patched (Ptc), Smoothened (Smo), Ihog (known as CDO or CDON in mammals) and the vertebrate-specific proteins Hip (also known as Hhip) and Gas1 (ref. 11). Drosophila Ihog and its vertebrate homologues CDO and BOC contain multiple immunoglobulin and fibronectin type III (FNIII) repeats, and the first FNIII repeat of Ihog binds Drosophila HhN in a heparin-dependent manner. Surprisingly, pull-down experiments suggest that a mammalian Sonic hedgehog N-terminal domain (ShhN) binds a non-orthologous FNIII repeat of CDO. Here we report biochemical, biophysical and X-ray structural studies of a complex between ShhN and the third FNIII repeat of CDO. We show that the ShhN-CDO interaction is completely unlike the HhN-Ihog interaction and requires calcium, which binds at a previously undetected site on ShhN. This site is conserved in nearly all Hh proteins and is a hotspot for mediating interactions between ShhN and CDO, Ptc, Hip and Gas1. Mutations in vertebrate Hh proteins causing holoprosencephaly and brachydactyly type A1 map to this calcium-binding site and disrupt interactions with these partners.

The mode of Hedgehog binding to Ihog homologues is not conserved across different phyla.,McLellan JS, Zheng X, Hauk G, Ghirlando R, Beachy PA, Leahy DJ Nature. 2008 Oct 16;455(7215):979-83. Epub 2008 Sep 14. PMID:18794898^[2]

From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine.

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
↑ McLellan JS, Zheng X, Hauk G, Ghirlando R, Beachy PA, Leahy DJ. The mode of Hedgehog binding to Ihog homologues is not conserved across different phyla. Nature. 2008 Oct 16;455(7215):979-83. Epub 2008 Sep 14. PMID:18794898 doi:10.1038/nature07358

1 Structural highlights
2 Disease
3 Function
4 Evolutionary Conservation
5 Publication Abstract from PubMed
6 References

Proteopedia Page Contributors and Editors (what is this?)

OCA

Retrieved from "http://52.214.119.220/wiki/index.php/3d1m"

@@ Line 1: / Line 1: @@
 ==Crystal Structure of Sonic Hedgehog Bound to the third FNIII domain of CDO==
 <StructureSection load='3d1m' size='340' side='right' caption='[[3d1m]], [[Resolution|resolution]] 1.70&Aring;' scene=''>
@@ Line 5: / Line 6: @@
 </td></tr><tr id='ligand'><td class="sblockLbl"><b>[[Ligand|Ligands:]]</b></td><td class="sblockDat"><scene name='pdbligand=CA:CALCIUM+ION'>CA</scene>, <scene name='pdbligand=ZN:ZINC+ION'>ZN</scene></td></tr>
 <tr id='gene'><td class="sblockLbl"><b>[[Gene|Gene:]]</b></td><td class="sblockDat">Shh, Hhg1 ([http://www.ncbi.nlm.nih.gov/Taxonomy/Browser/wwwtax.cgi?mode=Info&srchmode=5&id=10090 LK3 transgenic mice]), CDON, CDO ([http://www.ncbi.nlm.nih.gov/Taxonomy/Browser/wwwtax.cgi?mode=Info&srchmode=5&id=9606 HUMAN])</td></tr>
-<tr id='resources'><td class="sblockLbl"><b>Resources:</b></td><td class="sblockDat"><span class='plainlinks'>[http://oca.weizmann.ac.il/oca-docs/fgij/fg.htm?mol=3d1m FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=3d1m OCA], [http://pdbe.org/3d1m PDBe], [http://www.rcsb.org/pdb/explore.do?structureId=3d1m RCSB], [http://www.ebi.ac.uk/pdbsum/3d1m PDBsum]</span></td></tr>
+<tr id='resources'><td class="sblockLbl"><b>Resources:</b></td><td class="sblockDat"><span class='plainlinks'>[http://oca.weizmann.ac.il/oca-docs/fgij/fg.htm?mol=3d1m FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=3d1m OCA], [http://pdbe.org/3d1m PDBe], [http://www.rcsb.org/pdb/explore.do?structureId=3d1m RCSB], [http://www.ebi.ac.uk/pdbsum/3d1m PDBsum], [http://prosat.h-its.org/prosat/prosatexe?pdbcode=3d1m ProSAT]</span></td></tr>
 </table>
 == Disease ==

3d1m

From Proteopedia

Revision as of 08:40, 25 October 2017

Crystal Structure of Sonic Hedgehog Bound to the third FNIII domain of CDO

Structural highlights

Disease

Function

Evolutionary Conservation

Publication Abstract from PubMed

References

Contents

Proteopedia Page Contributors and Editors (what is this?)

Views

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