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| | ==High Resolution Crystal Structure of the EGF domain of Spitz== | | ==High Resolution Crystal Structure of the EGF domain of Spitz== |
| - | <StructureSection load='3ca7' size='340' side='right' caption='[[3ca7]], [[Resolution|resolution]] 1.50Å' scene=''> | + | <StructureSection load='3ca7' size='340' side='right'caption='[[3ca7]], [[Resolution|resolution]] 1.50Å' scene=''> |
| | == Structural highlights == | | == Structural highlights == |
| - | <table><tr><td colspan='2'>[[3ca7]] is a 1 chain structure with sequence from [http://en.wikipedia.org/wiki/Drosophila_melanogaster Drosophila melanogaster]. Full crystallographic information is available from [http://oca.weizmann.ac.il/oca-bin/ocashort?id=3CA7 OCA]. For a <b>guided tour on the structure components</b> use [http://oca.weizmann.ac.il/oca-docs/fgij/fg.htm?mol=3CA7 FirstGlance]. <br> | + | <table><tr><td colspan='2'>[[3ca7]] is a 1 chain structure with sequence from [https://en.wikipedia.org/wiki/Drosophila_melanogaster Drosophila melanogaster]. Full crystallographic information is available from [http://oca.weizmann.ac.il/oca-bin/ocashort?id=3CA7 OCA]. For a <b>guided tour on the structure components</b> use [https://proteopedia.org/fgij/fg.htm?mol=3CA7 FirstGlance]. <br> |
| - | </td></tr><tr id='gene'><td class="sblockLbl"><b>[[Gene|Gene:]]</b></td><td class="sblockDat">spi ([http://www.ncbi.nlm.nih.gov/Taxonomy/Browser/wwwtax.cgi?mode=Info&srchmode=5&id=7227 Drosophila melanogaster])</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]] 1.5Å</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=3ca7 FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=3ca7 OCA], [http://pdbe.org/3ca7 PDBe], [http://www.rcsb.org/pdb/explore.do?structureId=3ca7 RCSB], [http://www.ebi.ac.uk/pdbsum/3ca7 PDBsum], [http://prosat.h-its.org/prosat/prosatexe?pdbcode=3ca7 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=3ca7 FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=3ca7 OCA], [https://pdbe.org/3ca7 PDBe], [https://www.rcsb.org/pdb/explore.do?structureId=3ca7 RCSB], [https://www.ebi.ac.uk/pdbsum/3ca7 PDBsum], [https://prosat.h-its.org/prosat/prosatexe?pdbcode=3ca7 ProSAT]</span></td></tr> |
| | </table> | | </table> |
| | == Function == | | == Function == |
| - | [[http://www.uniprot.org/uniprot/SPITZ_DROME SPITZ_DROME]] Ligand for the EGF receptor (Gurken). Involved in a number of unrelated developmental choices, for example, dorsal-ventral axis formation, glial migration, sensory organ determination, and muscle development. It is required for photoreceptor determination.<ref>PMID:7833286</ref> | + | [https://www.uniprot.org/uniprot/SPITZ_DROME SPITZ_DROME] Ligand for the EGF receptor (Gurken). Involved in a number of unrelated developmental choices, for example, dorsal-ventral axis formation, glial migration, sensory organ determination, and muscle development. It is required for photoreceptor determination.<ref>PMID:7833286</ref> |
| | == Evolutionary Conservation == | | == Evolutionary Conservation == |
| | [[Image:Consurf_key_small.gif|200px|right]] | | [[Image:Consurf_key_small.gif|200px|right]] |
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| | <jmolCheckbox> | | <jmolCheckbox> |
| | <scriptWhenChecked>; select protein; define ~consurf_to_do selected; consurf_initial_scene = true; script "/wiki/ConSurf/ca/3ca7_consurf.spt"</scriptWhenChecked> | | <scriptWhenChecked>; select protein; define ~consurf_to_do selected; consurf_initial_scene = true; script "/wiki/ConSurf/ca/3ca7_consurf.spt"</scriptWhenChecked> |
| - | <scriptWhenUnchecked>script /wiki/extensions/Proteopedia/spt/initialview01.spt</scriptWhenUnchecked> | + | <scriptWhenUnchecked>script /wiki/extensions/Proteopedia/spt/initialview03.spt</scriptWhenUnchecked> |
| | <text>to colour the structure by Evolutionary Conservation</text> | | <text>to colour the structure by Evolutionary Conservation</text> |
| | </jmolCheckbox> | | </jmolCheckbox> |
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| | </StructureSection> | | </StructureSection> |
| | [[Category: Drosophila melanogaster]] | | [[Category: Drosophila melanogaster]] |
| - | [[Category: Klein, D E]] | + | [[Category: Large Structures]] |
| - | [[Category: Lemmon, M A]] | + | [[Category: Klein DE]] |
| - | [[Category: Stayrook, S E]] | + | [[Category: Lemmon MA]] |
| - | [[Category: Argo]] | + | [[Category: Stayrook SE]] |
| - | [[Category: Developmental protein]]
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| - | [[Category: Differentiation]]
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| - | [[Category: Egf]]
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| - | [[Category: Egf-like domain]]
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| - | [[Category: Endoplasmic reticulum]]
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| - | [[Category: Glycoprotein]]
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| - | [[Category: Golgi apparatus]]
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| - | [[Category: Hormone-signaling protein complex]]
| + | |
| - | [[Category: Membrane]]
| + | |
| - | [[Category: Neurogenesis]]
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| - | [[Category: Spitz]]
| + | |
| - | [[Category: Transmembrane]]
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| Structural highlights
Function
SPITZ_DROME Ligand for the EGF receptor (Gurken). Involved in a number of unrelated developmental choices, for example, dorsal-ventral axis formation, glial migration, sensory organ determination, and muscle development. It is required for photoreceptor determination.[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
Members of the epidermal growth factor receptor (EGFR) or ErbB/HER family and their activating ligands are essential regulators of diverse developmental processes. Inappropriate activation of these receptors is a key feature of many human cancers, and its reversal is an important clinical goal. A natural secreted antagonist of EGFR signalling, called Argos, was identified in Drosophila. We showed previously that Argos functions by directly binding (and sequestering) growth factor ligands that activate EGFR. Here we describe the 1.6-A resolution crystal structure of Argos bound to an EGFR ligand. Contrary to expectations, Argos contains no EGF-like domain. Instead, a trio of closely related domains (resembling a three-finger toxin fold) form a clamp-like structure around the bound EGF ligand. Although structurally unrelated to the receptor, Argos mimics EGFR by using a bipartite binding surface to entrap EGF. The individual Argos domains share unexpected structural similarities with the extracellular ligand-binding regions of transforming growth factor-beta family receptors. The three-domain clamp of Argos also resembles the urokinase-type plasminogen activator (uPA) receptor, which uses a similar mechanism to engulf the EGF-like module of uPA. Our results indicate that undiscovered mammalian counterparts of Argos may exist among other poorly characterized structural homologues. In addition, the structures presented here define requirements for the design of artificial EGF-sequestering proteins that would be valuable anti-cancer therapeutics.
Structural basis for EGFR ligand sequestration by Argos.,Klein DE, Stayrook SE, Shi F, Narayan K, Lemmon MA Nature. 2008 Jun 26;453(7199):1271-5. Epub 2008 May 25. PMID:18500331[2]
From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine.
References
- ↑ Freeman M. The spitz gene is required for photoreceptor determination in the Drosophila eye where it interacts with the EGF receptor. Mech Dev. 1994 Oct;48(1):25-33. PMID:7833286
- ↑ Klein DE, Stayrook SE, Shi F, Narayan K, Lemmon MA. Structural basis for EGFR ligand sequestration by Argos. Nature. 2008 Jun 26;453(7199):1271-5. Epub 2008 May 25. PMID:18500331 doi:10.1038/nature06978
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