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| | ==Crystal structure of Down Syndrome Cell Adhesion Molecule (DSCAM) isoform 1.30.30, N-terminal eight Ig domains== | | ==Crystal structure of Down Syndrome Cell Adhesion Molecule (DSCAM) isoform 1.30.30, N-terminal eight Ig domains== |
| - | <StructureSection load='3dmk' size='340' side='right' caption='[[3dmk]], [[Resolution|resolution]] 4.19Å' scene=''> | + | <StructureSection load='3dmk' size='340' side='right'caption='[[3dmk]], [[Resolution|resolution]] 4.19Å' scene=''> |
| | == Structural highlights == | | == Structural highlights == |
| - | <table><tr><td colspan='2'>[[3dmk]] is a 3 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=3DMK OCA]. For a <b>guided tour on the structure components</b> use [http://oca.weizmann.ac.il/oca-docs/fgij/fg.htm?mol=3DMK FirstGlance]. <br> | + | <table><tr><td colspan='2'>[[3dmk]] is a 3 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=3DMK OCA]. For a <b>guided tour on the structure components</b> use [https://proteopedia.org/fgij/fg.htm?mol=3DMK FirstGlance]. <br> |
| - | </td></tr><tr id='ligand'><td class="sblockLbl"><b>[[Ligand|Ligands:]]</b></td><td class="sblockDat"><scene name='pdbligand=GOL:GLYCEROL'>GOL</scene>, <scene name='pdbligand=SO4:SULFATE+ION'>SO4</scene>, <scene name='pdbligand=NAG:N-ACETYL-D-GLUCOSAMINE'>NAG</scene>, <scene name='pdbligand=NDG:2-(ACETYLAMINO)-2-DEOXY-A-D-GLUCOPYRANOSE'>NDG</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]] 4.19Å</td></tr> |
| - | <tr id='related'><td class="sblockLbl"><b>[[Related_structure|Related:]]</b></td><td class="sblockDat">[[2v5m|2v5m]], [[2v5r|2v5r]], [[2v5s|2v5s]]</td></tr> | + | <tr id='ligand'><td class="sblockLbl"><b>[[Ligand|Ligands:]]</b></td><td class="sblockDat" id="ligandDat"><scene name='pdbligand=GOL:GLYCEROL'>GOL</scene>, <scene name='pdbligand=NAG:N-ACETYL-D-GLUCOSAMINE'>NAG</scene>, <scene name='pdbligand=SO4:SULFATE+ION'>SO4</scene></td></tr> |
| - | <tr id='gene'><td class="sblockLbl"><b>[[Gene|Gene:]]</b></td><td class="sblockDat">Dscam ([http://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=3dmk FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=3dmk OCA], [https://pdbe.org/3dmk PDBe], [https://www.rcsb.org/pdb/explore.do?structureId=3dmk RCSB], [https://www.ebi.ac.uk/pdbsum/3dmk PDBsum], [https://prosat.h-its.org/prosat/prosatexe?pdbcode=3dmk 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=3dmk FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=3dmk OCA], [http://www.rcsb.org/pdb/explore.do?structureId=3dmk RCSB], [http://www.ebi.ac.uk/pdbsum/3dmk PDBsum]</span></td></tr> | + | |
| | </table> | | </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 == | | == Evolutionary Conservation == |
| | [[Image:Consurf_key_small.gif|200px|right]] | | [[Image:Consurf_key_small.gif|200px|right]] |
| | Check<jmol> | | Check<jmol> |
| | <jmolCheckbox> | | <jmolCheckbox> |
| - | <scriptWhenChecked>select protein; define ~consurf_to_do selected; consurf_initial_scene = true; script "/wiki/ConSurf/dm/3dmk_consurf.spt"</scriptWhenChecked> | + | <scriptWhenChecked>; select protein; define ~consurf_to_do selected; consurf_initial_scene = true; script "/wiki/ConSurf/dm/3dmk_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> |
| - | </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]. | + | </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=3dmk ConSurf]. |
| | <div style="clear:both"></div> | | <div style="clear:both"></div> |
| | <div style="background-color:#fffaf0;"> | | <div style="background-color:#fffaf0;"> |
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| | From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine.<br> | | From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine.<br> |
| | </div> | | </div> |
| | + | <div class="pdbe-citations 3dmk" style="background-color:#fffaf0;"></div> |
| | == References == | | == References == |
| | <references/> | | <references/> |
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| | </StructureSection> | | </StructureSection> |
| | [[Category: Drosophila melanogaster]] | | [[Category: Drosophila melanogaster]] |
| - | [[Category: Eisenberg, D]] | + | [[Category: Large Structures]] |
| - | [[Category: Sawaya, M R]] | + | [[Category: Eisenberg D]] |
| - | [[Category: Wojtowicz, W M]] | + | [[Category: Sawaya MR]] |
| - | [[Category: Zipursky, S L]] | + | [[Category: Wojtowicz WM]] |
| - | [[Category: Cell adhesion]] | + | [[Category: Zipursky SL]] |
| - | [[Category: Ig domain]]
| + | |
| - | [[Category: Immunoglobulin domain]]
| + | |
| Structural highlights
Function
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).[1] [2] [3] [4] [5] [6] [7] [8]
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
Drosophila Dscam encodes a vast family of immunoglobulin (Ig)-containing proteins that exhibit isoform-specific homophilic binding. This diversity is essential for cell recognition events required for wiring the brain. Each isoform binds to itself but rarely to other isoforms. Specificity is determined by "matching" of three variable Ig domains within an approximately 220 kD ectodomain. Here, we present the structure of the homophilic binding region of Dscam, comprising the eight N-terminal Ig domains (Dscam(1-8)). Dscam(1-8) forms a symmetric homodimer of S-shaped molecules. This conformation, comprising two reverse turns, allows each pair of the three variable domains to "match" in an antiparallel fashion. Structural, genetic, and biochemical studies demonstrate that, in addition to variable domain "matching," intramolecular interactions between constant domains promote homophilic binding. These studies provide insight into how "matching" at all three pairs of variable domains in Dscam mediates isoform-specific recognition.
A double S shape provides the structural basis for the extraordinary binding specificity of Dscam isoforms.,Sawaya MR, Wojtowicz WM, Andre I, Qian B, Wu W, Baker D, Eisenberg D, Zipursky SL Cell. 2008 Sep 19;134(6):1007-18. PMID:18805093[9]
From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine.
References
- ↑ Schmucker D, Clemens JC, Shu H, Worby CA, Xiao J, Muda M, Dixon JE, Zipursky SL. Drosophila Dscam is an axon guidance receptor exhibiting extraordinary molecular diversity. Cell. 2000 Jun 9;101(6):671-84. PMID:10892653 doi:10.1016/s0092-8674(00)80878-8
- ↑ Wang J, Zugates CT, Liang IH, Lee CH, Lee T. Drosophila Dscam is required for divergent segregation of sister branches and suppresses ectopic bifurcation of axons. Neuron. 2002 Feb 14;33(4):559-71. PMID:11856530 doi:10.1016/s0896-6273(02)00570-6
- ↑ Neves G, Zucker J, Daly M, Chess A. Stochastic yet biased expression of multiple Dscam splice variants by individual cells. Nat Genet. 2004 Mar;36(3):240-6. PMID:14758360 doi:10.1038/ng1299
- ↑ Wang J, Ma X, Yang JS, Zheng X, Zugates CT, Lee CH, Lee T. Transmembrane/juxtamembrane domain-dependent Dscam distribution and function during mushroom body neuronal morphogenesis. Neuron. 2004 Sep 2;43(5):663-72. PMID:15339648 doi:10.1016/j.neuron.2004.06.033
- ↑ Wojtowicz WM, Flanagan JJ, Millard SS, Zipursky SL, Clemens JC. Alternative splicing of Drosophila Dscam generates axon guidance receptors that exhibit isoform-specific homophilic binding. Cell. 2004 Sep 3;118(5):619-33. PMID:15339666 doi:10.1016/j.cell.2004.08.021
- ↑ Watson FL, Püttmann-Holgado R, Thomas F, Lamar DL, Hughes M, Kondo M, Rebel VI, Schmucker D. Extensive diversity of Ig-superfamily proteins in the immune system of insects. Science. 2005 Sep 16;309(5742):1874-8. PMID:16109846 doi:10.1126/science.1116887
- ↑ Matthews BJ, Kim ME, Flanagan JJ, Hattori D, Clemens JC, Zipursky SL, Grueber WB. Dendrite self-avoidance is controlled by Dscam. Cell. 2007 May 4;129(3):593-604. PMID:17482551 doi:10.1016/j.cell.2007.04.013
- ↑ Wojtowicz WM, Wu W, Andre I, Qian B, Baker D, Zipursky SL. A vast repertoire of Dscam binding specificities arises from modular interactions of variable Ig domains. Cell. 2007 Sep 21;130(6):1134-45. PMID:17889655 doi:10.1016/j.cell.2007.08.026
- ↑ Sawaya MR, Wojtowicz WM, Andre I, Qian B, Wu W, Baker D, Eisenberg D, Zipursky SL. A double S shape provides the structural basis for the extraordinary binding specificity of Dscam isoforms. Cell. 2008 Sep 19;134(6):1007-18. PMID:18805093 doi:10.1016/j.cell.2008.07.042
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