View source for 3c9a


==High Resolution Crystal Structure of Argos bound to the EGF domain of Spitz==
<StructureSection load='3c9a' size='340' side='right'caption='[[3c9a]], [[Resolution|resolution]] 1.60&Aring;' scene=''>
== Structural highlights ==
<table><tr><td colspan='2'>[[3c9a]] is a 4 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=3C9A OCA]. For a <b>guided tour on the structure components</b> use [https://proteopedia.org/fgij/fg.htm?mol=3C9A FirstGlance]. <br>
</td></tr><tr id='ligand'><td class="sblockLbl"><b>[[Ligand|Ligands:]]</b></td><td class="sblockDat" id="ligandDat"><scene name='pdbligand=BR:BROMIDE+ION'>BR</scene></td></tr>
<tr id='related'><td class="sblockLbl"><b>[[Related_structure|Related:]]</b></td><td class="sblockDat"><div style='overflow: auto; max-height: 3em;'>[[3ca7|3ca7]], [[3cgu|3cgu]]</div></td></tr>
<tr id='gene'><td class="sblockLbl"><b>[[Gene|Gene:]]</b></td><td class="sblockDat">argos, Aos, gil, sty ([https://www.ncbi.nlm.nih.gov/Taxonomy/Browser/wwwtax.cgi?mode=Info&srchmode=5&id=7227 Drosophila melanogaster]), spi ([https://www.ncbi.nlm.nih.gov/Taxonomy/Browser/wwwtax.cgi?mode=Info&srchmode=5&id=7227 Drosophila melanogaster])</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=3c9a FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=3c9a OCA], [https://pdbe.org/3c9a PDBe], [https://www.rcsb.org/pdb/explore.do?structureId=3c9a RCSB], [https://www.ebi.ac.uk/pdbsum/3c9a PDBsum], [https://prosat.h-its.org/prosat/prosatexe?pdbcode=3c9a ProSAT]</span></td></tr>
</table>
== Function ==
[[https://www.uniprot.org/uniprot/GIL_DROME GIL_DROME]] Regulates cell determination; development of ommatidia and optic lobe. Is a signaling molecule involved in the process of axon pathfinding in the eye. Part of the Ras pathway regulating programmed cell death in pupal eyes; activated by lozenge (lz). Antagonist for the Egfr receptor (gurken). Inhibits Egfr signaling without interacting directly with the receptor, but instead by sequestering the Egfr-activating ligand spitz (spi).<ref>PMID:1628618</ref> <ref>PMID:1606617</ref> <ref>PMID:1286772</ref> <ref>PMID:10200472</ref> <ref>PMID:15329724</ref> <ref>PMID:15879554</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 ==
[[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/c9/3c9a_consurf.spt"</scriptWhenChecked>
    <scriptWhenUnchecked>script /wiki/extensions/Proteopedia/spt/initialview01.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=3c9a ConSurf].
<div style="clear:both"></div>
<div style="background-color:#fffaf0;">
== 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<ref>PMID:18500331</ref>

From MEDLINE&reg;/PubMed&reg;, a database of the U.S. National Library of Medicine.<br>
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<div class="pdbe-citations 3c9a" style="background-color:#fffaf0;"></div>
== References ==
<references/>
__TOC__
</StructureSection>
[[Category: Drosophila melanogaster]]
[[Category: Large Structures]]
[[Category: Klein, D E]]
[[Category: Lemmon, M A]]
[[Category: Narayan, K]]
[[Category: Shi, F]]
[[Category: Stayrook, S E]]
[[Category: Argo]]
[[Category: Developmental protein]]
[[Category: Differentiation]]
[[Category: Egf]]
[[Category: Egf-like domain]]
[[Category: Egfr inhibitor]]
[[Category: Endoplasmic reticulum]]
[[Category: Glycoprotein]]
[[Category: Golgi apparatus]]
[[Category: Hormone-signaling protein complex]]
[[Category: Inhibitor]]
[[Category: Membrane]]
[[Category: Neurogenesis]]
[[Category: Secreted]]
[[Category: Sensory transduction]]
[[Category: Spitz]]
[[Category: Transmembrane]]
[[Category: Vision]]