View source for 2v5s


==Structural basis for Dscam isoform specificity==
<StructureSection load='2v5s' size='340' side='right'caption='[[2v5s]], [[Resolution|resolution]] 2.30&Aring;' scene=''>
== Structural highlights ==
<table><tr><td colspan='2'>[[2v5s]] is a 2 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=2V5S OCA]. For a <b>guided tour on the structure components</b> use [https://proteopedia.org/fgij/fg.htm?mol=2V5S FirstGlance]. <br>
</td></tr><tr id='method'><td class="sblockLbl"><b>[[Empirical_models|Method:]]</b></td><td class="sblockDat" id="methodDat">X-ray diffraction, [[Resolution|Resolution]] 2.3&#8491;</td></tr>
<tr id='ligand'><td class="sblockLbl"><b>[[Ligand|Ligands:]]</b></td><td class="sblockDat" id="ligandDat"><scene name='pdbligand=NAG:N-ACETYL-D-GLUCOSAMINE'>NAG</scene></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=2v5s FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=2v5s OCA], [https://pdbe.org/2v5s PDBe], [https://www.rcsb.org/pdb/explore.do?structureId=2v5s RCSB], [https://www.ebi.ac.uk/pdbsum/2v5s PDBsum], [https://prosat.h-its.org/prosat/prosatexe?pdbcode=2v5s ProSAT]</span></td></tr>
</table>
== Function ==
[https://www.uniprot.org/uniprot/DSCA1_DROME DSCA1_DROME] Cell surface receptor involved in guidance and targeting of growing nerve axons (PubMed:10892653). Required during Bolwig's organ differentiation for accurate and efficient targeting of photoreceptor neuron axons to their synaptic targets in the brain via the P2 intermediate target neuron (PubMed:10892653). Involved in isoneural self-avoidance during dendrite arborization but not in heteroneural recognition and repulsion during tiling by related neurons of the same class (PubMed:17482551). Involved in regulating axon bifurcation and divergent extension in the developing mushroom body (PubMed:11856530, PubMed:15339648). Essential for axon arborisation in ellipsoid body (PubMed:11856530, PubMed:15339648). Exhibits an extraordinary level of molecular diversity resulting from alternative splicing (PubMed:10892653). Isoforms differing in their ectodomain makeup show a high degree of functional redundancy while isoforms with different transmembrane domains are involved in different neuronal morphogenetic processes and are differentially targeted to dendrites or axons (PubMed:15339648). The vast majority of isoforms exhibit strong isoform-specific homophilic binding (PubMed:15339666, PubMed:17889655). Individual cells express a distinct randomly generated repertoire of isoforms (PubMed:14758360). Cell surfaces bearing identical repertoires of Dscam1 isoforms, such as those from the same cell, trigger recognition and avoidance (PubMed:17482551). A subset of isoforms is expressed in fat body cells and hemocytes, cells that are part of the insect immune response, and these isoforms are secreted into the hemolymph (PubMed:16109846). The secreted form comprising the ectodomain can bind to bacteria, such as Escherichia coli, and may act as an opsonin enhancing their phagocytosis by hemocytes (PubMed:16109846).<ref>PMID:10892653</ref> <ref>PMID:11856530</ref> <ref>PMID:14758360</ref> <ref>PMID:15339648</ref> <ref>PMID:15339666</ref> <ref>PMID:16109846</ref> <ref>PMID:17482551</ref> <ref>PMID:17889655</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/v5/2v5s_consurf.spt"</scriptWhenChecked>
    <scriptWhenUnchecked>script /wiki/extensions/Proteopedia/spt/initialview03.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=2v5s ConSurf].
<div style="clear:both"></div>
<div style="background-color:#fffaf0;">
== Publication Abstract from PubMed ==
The Dscam gene gives rise to thousands of diverse cell surface receptors thought to provide homophilic and heterophilic recognition specificity for neuronal wiring and immune responses. Mutually exclusive splicing allows for the generation of sequence variability in three immunoglobulin ecto-domains, D2, D3 and D7. We report X-ray structures of the amino-terminal four immunoglobulin domains (D1-D4) of two distinct Dscam isoforms. The structures reveal a horseshoe configuration, with variable residues of D2 and D3 constituting two independent surface epitopes on either side of the receptor. Both isoforms engage in homo-dimerization coupling variable domain D2 with D2, and D3 with D3. These interactions involve symmetric, antiparallel pairing of identical peptide segments from epitope I that are unique to each isoform. Structure-guided mutagenesis and swapping of peptide segments confirm that epitope I, but not epitope II, confers homophilic binding specificity of full-length Dscam receptors. Phylogenetic analysis shows strong selection of matching peptide sequences only for epitope I. We propose that peptide complementarity of variable residues in epitope I of Dscam is essential for homophilic binding specificity.

Structural basis of Dscam isoform specificity.,Meijers R, Puettmann-Holgado R, Skiniotis G, Liu JH, Walz T, Wang JH, Schmucker D Nature. 2007 Sep 27;449(7161):487-91. Epub 2007 Aug 26. PMID:17721508<ref>PMID:17721508</ref>

From MEDLINE&reg;/PubMed&reg;, a database of the U.S. National Library of Medicine.<br>
</div>
<div class="pdbe-citations 2v5s" style="background-color:#fffaf0;"></div>
== References ==
<references/>
__TOC__
</StructureSection>
[[Category: Drosophila melanogaster]]
[[Category: Large Structures]]
[[Category: Liu J-H]]
[[Category: Meijers R]]
[[Category: Puettmann-Holgado R]]
[[Category: Schmucker D]]
[[Category: Skiniotis G]]
[[Category: Walz T]]
[[Category: Wang J-H]]