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| | ==Crystal Structure of DhhN bound to CDOFn3== | | ==Crystal Structure of DhhN bound to CDOFn3== |
| - | <StructureSection load='3n1q' size='340' side='right' caption='[[3n1q]], [[Resolution|resolution]] 2.89Å' scene=''> | + | <StructureSection load='3n1q' size='340' side='right'caption='[[3n1q]], [[Resolution|resolution]] 2.89Å' scene=''> |
| | == Structural highlights == | | == Structural highlights == |
| - | <table><tr><td colspan='2'>[[3n1q]] is a 6 chain structure with sequence from [http://en.wikipedia.org/wiki/Human Human]. Full crystallographic information is available from [http://oca.weizmann.ac.il/oca-bin/ocashort?id=3N1Q OCA]. For a <b>guided tour on the structure components</b> use [http://oca.weizmann.ac.il/oca-docs/fgij/fg.htm?mol=3N1Q FirstGlance]. <br> | + | <table><tr><td colspan='2'>[[3n1q]] is a 6 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=3N1Q OCA]. For a <b>guided tour on the structure components</b> use [https://proteopedia.org/fgij/fg.htm?mol=3N1Q FirstGlance]. <br> |
| - | </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> | + | </td></tr><tr id='method'><td class="sblockLbl"><b>[[Empirical_models|Method:]]</b></td><td class="sblockDat" id="methodDat">X-ray diffraction, [[Resolution|Resolution]] 2.89Å</td></tr> |
| - | <tr id='related'><td class="sblockLbl"><b>[[Related_structure|Related:]]</b></td><td class="sblockDat">[[3d1m|3d1m]], [[3n1f|3n1f]], [[3n1g|3n1g]], [[3n1m|3n1m]], [[3n1o|3n1o]], [[3n1p|3n1p]], [[3n1r|3n1r]]</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='gene'><td class="sblockLbl"><b>[[Gene|Gene:]]</b></td><td class="sblockDat">DHH ([http://www.ncbi.nlm.nih.gov/Taxonomy/Browser/wwwtax.cgi?mode=Info&srchmode=5&id=9606 HUMAN]), 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'>[https://proteopedia.org/fgij/fg.htm?mol=3n1q FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=3n1q OCA], [https://pdbe.org/3n1q PDBe], [https://www.rcsb.org/pdb/explore.do?structureId=3n1q RCSB], [https://www.ebi.ac.uk/pdbsum/3n1q PDBsum], [https://prosat.h-its.org/prosat/prosatexe?pdbcode=3n1q ProSAT]</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=3n1q FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=3n1q OCA], [http://pdbe.org/3n1q PDBe], [http://www.rcsb.org/pdb/explore.do?structureId=3n1q RCSB], [http://www.ebi.ac.uk/pdbsum/3n1q PDBsum], [http://prosat.h-its.org/prosat/prosatexe?pdbcode=3n1q ProSAT]</span></td></tr> | + | |
| | </table> | | </table> |
| | == Disease == | | == Disease == |
| - | [[http://www.uniprot.org/uniprot/DHH_HUMAN DHH_HUMAN]] Defects in DHH may be the cause of partial gonadal dysgenesis with minifascicular neuropathy 46,XY (PGD) [MIM:[http://omim.org/entry/607080 607080]]. PGD is characterized by the presence of a testis on one side and a streak or an absent gonad at the other, persistence of Muellerian duct structures, and a variable degree of genital ambiguity.<ref>PMID:11017805</ref> Defects in DHH may be the cause of complete pure gonadal dysgenesis 46,XY type (GDXYM) [MIM:[http://omim.org/entry/233420 233420]]; also known as male-limited gonadal dysgenesis 46,XY. GDXYM is a type of hypogonadism in which no functional gonads are present to induce puberty in an externally female person whose karyotype is then found to be XY. The gonads are found to be non-functional streaks.<ref>PMID:15356051</ref> [[http://www.uniprot.org/uniprot/CDON_HUMAN CDON_HUMAN]] Defects in CDON are the cause of holoprosencephaly type 11 (HPE11) [MIM:[http://omim.org/entry/614226 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. | + | [https://www.uniprot.org/uniprot/DHH_HUMAN DHH_HUMAN] Defects in DHH may be the cause of partial gonadal dysgenesis with minifascicular neuropathy 46,XY (PGD) [MIM:[https://omim.org/entry/607080 607080]. PGD is characterized by the presence of a testis on one side and a streak or an absent gonad at the other, persistence of Muellerian duct structures, and a variable degree of genital ambiguity.<ref>PMID:11017805</ref> Defects in DHH may be the cause of complete pure gonadal dysgenesis 46,XY type (GDXYM) [MIM:[https://omim.org/entry/233420 233420]; also known as male-limited gonadal dysgenesis 46,XY. GDXYM is a type of hypogonadism in which no functional gonads are present to induce puberty in an externally female person whose karyotype is then found to be XY. The gonads are found to be non-functional streaks.<ref>PMID:15356051</ref> |
| | == Function == | | == Function == |
| - | [[http://www.uniprot.org/uniprot/DHH_HUMAN DHH_HUMAN]] Intercellular signal essential for a variety of patterning events during development. May function as a spermatocyte survival factor in the testes. Essential for testes development. [[http://www.uniprot.org/uniprot/CDON_HUMAN 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). | + | [https://www.uniprot.org/uniprot/DHH_HUMAN DHH_HUMAN] Intercellular signal essential for a variety of patterning events during development. May function as a spermatocyte survival factor in the testes. Essential for testes development. |
| | == Evolutionary Conservation == | | == Evolutionary Conservation == |
| | [[Image:Consurf_key_small.gif|200px|right]] | | [[Image:Consurf_key_small.gif|200px|right]] |
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| | __TOC__ | | __TOC__ |
| | </StructureSection> | | </StructureSection> |
| - | [[Category: Human]] | + | [[Category: Homo sapiens]] |
| - | [[Category: Kavran, J M]] | + | [[Category: Large Structures]] |
| - | [[Category: Leahy, D J]] | + | [[Category: Kavran JM]] |
| - | [[Category: Binding site]] | + | [[Category: Leahy DJ]] |
| - | [[Category: Calcium]]
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| - | [[Category: Cell adhesion molecule]]
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| - | [[Category: Cell cycle protein]]
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| - | [[Category: Cell line]]
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| - | [[Category: Cell surface]]
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| - | [[Category: Conserved sequence]]
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| - | [[Category: Fibronectin]]
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| - | [[Category: Hedgehog protein]]
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| - | [[Category: Immunoglobulin g]]
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| - | [[Category: Membrane glycoprotein]]
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| - | [[Category: Membrane protein]]
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| - | [[Category: Protein binding]]
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| - | [[Category: Receptor]]
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| - | [[Category: Sequence homology]]
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| - | [[Category: Signal transduction]]
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| - | [[Category: Tertiary]]
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| - | [[Category: Tumor suppressor protein]]
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| Structural highlights
Disease
DHH_HUMAN Defects in DHH may be the cause of partial gonadal dysgenesis with minifascicular neuropathy 46,XY (PGD) [MIM:607080. PGD is characterized by the presence of a testis on one side and a streak or an absent gonad at the other, persistence of Muellerian duct structures, and a variable degree of genital ambiguity.[1] Defects in DHH may be the cause of complete pure gonadal dysgenesis 46,XY type (GDXYM) [MIM:233420; also known as male-limited gonadal dysgenesis 46,XY. GDXYM is a type of hypogonadism in which no functional gonads are present to induce puberty in an externally female person whose karyotype is then found to be XY. The gonads are found to be non-functional streaks.[2]
Function
DHH_HUMAN Intercellular signal essential for a variety of patterning events during development. May function as a spermatocyte survival factor in the testes. Essential for testes development.
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) signaling proteins stimulate cell proliferation, differentiation, and tissue patterning at multiple points in animal development. A single Hh homolog is present in Drosophila, but three Hh homologs, Sonic Hh, Indian Hh, and Desert Hh, are present in mammals. Distribution, movement, and reception of Hh signals are tightly regulated, and abnormal Hh signaling is associated with developmental defects and cancer. In addition to the integral membrane proteins Patched and Smoothened, members of the Drosophila Ihog family of adhesion-like molecules have recently been shown to bind Hh proteins with micromolar affinity and positively regulate Hh signaling. Cell adhesion molecule-related, down-regulated by oncogenes (CDO) and Brother of CDO (BOC) are the closest mammalian relatives of Drosophila Ihog, and CDO binds Sonic Hh with micromolar affinity and positively regulates Hh signaling. Despite these similarities, structural and biochemical studies have shown that Ihog and CDO utilize nonorthologous domains and completely different binding modes to interact with cognate Hh proteins. We report here biochemical and x-ray structural studies of Sonic, Indian, and Desert Hh proteins both alone and complexed with active domains of CDO and BOC. These results show that all mammalian Hh proteins bind CDO and BOC in the same manner. We also show that interactions between Hh proteins and CDO are weakened at low pH. Formation of Hh-mediated Hh oligomers is thought to be an important feature of normal Hh signaling, but no conserved self-interaction between Hh proteins is apparent from inspection of 14 independent Hh-containing crystal lattices.
All mammalian Hedgehog proteins interact with cell adhesion molecule, down-regulated by oncogenes (CDO) and brother of CDO (BOC) in a conserved manner.,Kavran JM, Ward MD, Oladosu OO, Mulepati S, Leahy DJ J Biol Chem. 2010 Aug 6;285(32):24584-90. Epub 2010 Jun 1. PMID:20519495[3]
From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine.
References
- ↑ Umehara F, Tate G, Itoh K, Yamaguchi N, Douchi T, Mitsuya T, Osame M. A novel mutation of desert hedgehog in a patient with 46,XY partial gonadal dysgenesis accompanied by minifascicular neuropathy. Am J Hum Genet. 2000 Nov;67(5):1302-5. Epub 2000 Oct 2. PMID:11017805 doi:S0002-9297(07)62958-9
- ↑ Canto P, Soderlund D, Reyes E, Mendez JP. Mutations in the desert hedgehog (DHH) gene in patients with 46,XY complete pure gonadal dysgenesis. J Clin Endocrinol Metab. 2004 Sep;89(9):4480-3. PMID:15356051 doi:10.1210/jc.2004-0863
- ↑ Kavran JM, Ward MD, Oladosu OO, Mulepati S, Leahy DJ. All mammalian Hedgehog proteins interact with cell adhesion molecule, down-regulated by oncogenes (CDO) and brother of CDO (BOC) in a conserved manner. J Biol Chem. 2010 Aug 6;285(32):24584-90. Epub 2010 Jun 1. PMID:20519495 doi:10.1074/jbc.M110.131680
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