2v5m: Difference between revisions

Revision as of 18:12, 4 May 2008

STRUCTURAL BASIS FOR DSCAM ISOFORM SPECIFICITY

OverviewOverview

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.

About this StructureAbout this Structure

2V5M is a Single protein structure of sequence from Drosophila melanogaster. Full crystallographic information is available from OCA.

ReferenceReference

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 Page seeded by OCA on Sun May 4 18:12:57 2008

Proteopedia Page Contributors and Editors (what is this?)Proteopedia Page Contributors and Editors (what is this?)

OCA

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 [[Image:2v5m.jpg|left|200px]]
- {{Structure
+<!--
-|PDB= 2v5m |SIZE=350|CAPTION= <scene name='initialview01'>2v5m</scene>, resolution 1.95&Aring;
+The line below this paragraph, containing "STRUCTURE_2v5m", creates the "Structure Box" on the page.
-|SITE= <scene name='pdbsite=AC1:Gol+Binding+Site+For+Chain+A'>AC1</scene>
+You may change the PDB parameter (which sets the PDB file loaded into the applet)
-|LIGAND= <scene name='pdbligand=GOL:GLYCEROL'>GOL</scene>, <scene name='pdbligand=NAG:N-ACETYL-D-GLUCOSAMINE'>NAG</scene>
+or the SCENE parameter (which sets the initial scene displayed when the page is loaded),
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-|GENE=
+-->
-|DOMAIN=
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-|RELATEDENTRY=
-|RESOURCES=<span class='plainlinks'>[http://oca.weizmann.ac.il/oca-docs/fgij/fg.htm?mol=2v5m FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=2v5m OCA], [http://www.ebi.ac.uk/pdbsum/2v5m PDBsum], [http://www.rcsb.org/pdb/explore.do?structureId=2v5m RCSB]</span>
-}}
 '''STRUCTURAL BASIS FOR DSCAM ISOFORM SPECIFICITY'''
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 [[Category: Walz, T.]]
 [[Category: Wang, J H.]]
-[[Category: cell adhesion]]
+[[Category: Cell adhesion]]
-[[Category: developmental protein]]
+[[Category: Developmental protein]]
-[[Category: down syndrome cell adhesion molecule dscam]]
+[[Category: Down syndrome cell adhesion molecule dscam]]
-[[Category: immunoglobulin domain]]
+[[Category: Immunoglobulin domain]]
-[[Category: membrane]]
+[[Category: Membrane]]
-[[Category: neurobiology spl]]
+[[Category: Neurobiology spl]]
+''Page seeded by [http://oca.weizmann.ac.il/oca OCA ] on Sun May  4 18:12:57 2008''
-''Page seeded by [http://oca.weizmann.ac.il/oca OCA ] on Mon Mar 31 05:08:29 2008''