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3fub

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{{STRUCTURE_3fub| PDB=3fub | SCENE= }}
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==Crystal structure of GDNF-GFRalpha1 complex==
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===Crystal structure of GDNF-GFRalpha1 complex===
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<StructureSection load='3fub' size='340' side='right' caption='[[3fub]], [[Resolution|resolution]] 2.35&Aring;' scene=''>
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{{ABSTRACT_PUBMED_19478429}}
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== Structural highlights ==
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<table><tr><td colspan='2'>[[3fub]] is a 4 chain structure with sequence from [http://en.wikipedia.org/wiki/Homo_sapiens Homo sapiens] and [http://en.wikipedia.org/wiki/Rattus_norvegicus Rattus norvegicus]. Full crystallographic information is available from [http://oca.weizmann.ac.il/oca-bin/ocashort?id=3FUB OCA]. For a <b>guided tour on the structure components</b> use [http://oca.weizmann.ac.il/oca-docs/fgij/fg.htm?mol=3FUB FirstGlance]. <br>
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</td></tr><tr id='ligand'><td class="sblockLbl"><b>[[Ligand|Ligands:]]</b></td><td class="sblockDat"><scene name='pdbligand=EDO:1,2-ETHANEDIOL'>EDO</scene>, <scene name='pdbligand=NAG:N-ACETYL-D-GLUCOSAMINE'>NAG</scene>, <scene name='pdbligand=SO4:SULFATE+ION'>SO4</scene></td></tr>
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<tr id='related'><td class="sblockLbl"><b>[[Related_structure|Related:]]</b></td><td class="sblockDat">[[2v5e|2v5e]], [[2gh0|2gh0]]</td></tr>
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<tr id='gene'><td class="sblockLbl"><b>[[Gene|Gene:]]</b></td><td class="sblockDat">GDNF ([http://www.ncbi.nlm.nih.gov/Taxonomy/Browser/wwwtax.cgi?mode=Info&srchmode=5&id=9606 Homo sapiens])</td></tr>
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<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=3fub FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=3fub OCA], [http://www.rcsb.org/pdb/explore.do?structureId=3fub RCSB], [http://www.ebi.ac.uk/pdbsum/3fub PDBsum]</span></td></tr>
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</table>
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== Disease ==
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[[http://www.uniprot.org/uniprot/GDNF_HUMAN GDNF_HUMAN]] Defects in GDNF may be a cause of Hirschsprung disease type 3 (HSCR3) [MIM:[http://omim.org/entry/613711 613711]]. In association with mutations of RET gene, defects in GDNF may be involved in Hirschsprung disease. This genetic disorder of neural crest development is characterized by the absence of intramural ganglion cells in the hindgut, often resulting in intestinal obstruction.<ref>PMID:8968758</ref> <ref>PMID:8896568</ref> <ref>PMID:8896569</ref> <ref>PMID:10917288</ref> Defects in GDNF are a cause of congenital central hypoventilation syndrome (CCHS) [MIM:[http://omim.org/entry/209880 209880]]; also known as congenital failure of autonomic control or Ondine curse. CCHS is a rare disorder characterized by abnormal control of respiration in the absence of neuromuscular or lung disease, or an identifiable brain stem lesion. A deficiency in autonomic control of respiration results in inadequate or negligible ventilatory and arousal responses to hypercapnia and hypoxemia.<ref>PMID:9497256</ref>
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== Function ==
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[[http://www.uniprot.org/uniprot/GFRA1_RAT GFRA1_RAT]] Receptor for GDNF. Mediates the GDNF-induced autophosphorylation and activation of the RET receptor. [[http://www.uniprot.org/uniprot/GDNF_HUMAN GDNF_HUMAN]] Neurotrophic factor that enhances survival and morphological differentiation of dopaminergic neurons and increases their high-affinity dopamine uptake.<ref>PMID:8493557</ref>
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== Evolutionary Conservation ==
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[[Image:Consurf_key_small.gif|200px|right]]
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Check<jmol>
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<jmolCheckbox>
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<scriptWhenChecked>select protein; define ~consurf_to_do selected; consurf_initial_scene = true; script "/wiki/ConSurf/fu/3fub_consurf.spt"</scriptWhenChecked>
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<scriptWhenUnchecked>script /wiki/extensions/Proteopedia/spt/initialview01.spt</scriptWhenUnchecked>
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<text>to colour the structure by Evolutionary Conservation</text>
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</jmolCheckbox>
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</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/chain_selection.php?pdb_ID=2ata ConSurf].
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<div style="clear:both"></div>
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<div style="background-color:#fffaf0;">
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== Publication Abstract from PubMed ==
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Glial cell line-derived neurotrophic factor (GDNF) activates the receptor tyrosine kinase RET by binding to the GDNF-family receptor alpha1 (GFRalpha1) and forming the GDNF(2)-GFRalpha1(2)-RET(2) heterohexamer complex. A previous crystal structure of the GDNF(2)-GFRalpha1(2) complex (PDB code 2v5e) suggested that differences in signalling in GDNF-family ligand (GFL) complexes might arise from differences in the bend angle between the two monomers in the GFL homodimer. Here, a 2.35 A resolution structure of the GDNF(2)-GFRalpha1(2) complex crystallized with new cell dimensions is reported. The structure was refined to a final R factor of 22.5% (R(free) = 28%). The structures of both biological tetrameric complexes in the asymmetric unit are very similar to 2v5e and different from the artemin-GFRalpha3 structure, even though there is a small change in the structure of the GDNF. By comparison of all known GDNF and artemin structures, it is concluded that GDNF is more bent and more flexible than artemin and that this may be related to RET signalling. Comparisons also suggest that the differences between artemin and GDNF arise from the increased curvature of the artemin ;fingers', which both increases the buried surface area in the monomer-monomer interface and changes the intermonomer bend angle. From sequence comparison, it is suggested that neuturin (the second GFL) adopts an artemin-like conformation, while persephin has a different conformation to the other three.
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==Disease==
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Comparison of GFL-GFRalpha complexes: further evidence relating GFL bend angle to RET signalling.,Parkash V, Goldman A Acta Crystallogr Sect F Struct Biol Cryst Commun. 2009 Jun 1;65(Pt, 6):551-8. Epub 2009 May 23. PMID:19478429<ref>PMID:19478429</ref>
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[[http://www.uniprot.org/uniprot/GDNF_HUMAN GDNF_HUMAN]] Defects in GDNF may be a cause of Hirschsprung disease type 3 (HSCR3) [MIM:[http://omim.org/entry/613711 613711]]. In association with mutations of RET gene, defects in GDNF may be involved in Hirschsprung disease. This genetic disorder of neural crest development is characterized by the absence of intramural ganglion cells in the hindgut, often resulting in intestinal obstruction.<ref>PMID:8968758</ref><ref>PMID:8896568</ref><ref>PMID:8896569</ref><ref>PMID:10917288</ref> Defects in GDNF are a cause of congenital central hypoventilation syndrome (CCHS) [MIM:[http://omim.org/entry/209880 209880]]; also known as congenital failure of autonomic control or Ondine curse. CCHS is a rare disorder characterized by abnormal control of respiration in the absence of neuromuscular or lung disease, or an identifiable brain stem lesion. A deficiency in autonomic control of respiration results in inadequate or negligible ventilatory and arousal responses to hypercapnia and hypoxemia.<ref>PMID:9497256</ref>
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==Function==
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From MEDLINE&reg;/PubMed&reg;, a database of the U.S. National Library of Medicine.<br>
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[[http://www.uniprot.org/uniprot/GFRA1_RAT GFRA1_RAT]] Receptor for GDNF. Mediates the GDNF-induced autophosphorylation and activation of the RET receptor. [[http://www.uniprot.org/uniprot/GDNF_HUMAN GDNF_HUMAN]] Neurotrophic factor that enhances survival and morphological differentiation of dopaminergic neurons and increases their high-affinity dopamine uptake.<ref>PMID:8493557</ref>
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</div>
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== References ==
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==About this Structure==
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<references/>
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[[3fub]] is a 4 chain structure with sequence from [http://en.wikipedia.org/wiki/Homo_sapiens Homo sapiens] and [http://en.wikipedia.org/wiki/Rattus_norvegicus Rattus norvegicus]. Full crystallographic information is available from [http://oca.weizmann.ac.il/oca-bin/ocashort?id=3FUB OCA].
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__TOC__
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</StructureSection>
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==Reference==
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<ref group="xtra">PMID:019478429</ref><references group="xtra"/><references/>
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[[Category: Homo sapiens]]
[[Category: Homo sapiens]]
[[Category: Rattus norvegicus]]
[[Category: Rattus norvegicus]]
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[[Category: A., Goldman.]]
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[[Category: A., Goldman]]
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[[Category: V., Parkash.]]
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[[Category: V., Parkash]]
[[Category: All alpha gdnf]]
[[Category: All alpha gdnf]]
[[Category: Cell membrane]]
[[Category: Cell membrane]]

Revision as of 14:13, 18 December 2014

Crystal structure of GDNF-GFRalpha1 complex

3fub, resolution 2.35Å

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