6i9s

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(New page: '''Unreleased structure''' The entry 6i9s is ON HOLD Authors: Description: Category: Unreleased Structures)
Current revision (08:26, 20 March 2019) (edit) (undo)
 
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'''Unreleased structure'''
 
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The entry 6i9s is ON HOLD
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==hRobo2 Extracellular Domains 2-3==
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<StructureSection load='6i9s' size='340' side='right'caption='[[6i9s]], [[Resolution|resolution]] 2.48&Aring;' scene=''>
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== Structural highlights ==
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<table><tr><td colspan='2'>[[6i9s]] is a 2 chain structure with sequence from [http://en.wikipedia.org/wiki/Human Human]. Full crystallographic information is available from [http://oca.weizmann.ac.il/oca-bin/ocashort?id=6I9S OCA]. For a <b>guided tour on the structure components</b> use [http://oca.weizmann.ac.il/oca-docs/fgij/fg.htm?mol=6I9S FirstGlance]. <br>
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</td></tr><tr id='ligand'><td class="sblockLbl"><b>[[Ligand|Ligands:]]</b></td><td class="sblockDat"><scene name='pdbligand=NA:SODIUM+ION'>NA</scene></td></tr>
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<tr id='gene'><td class="sblockLbl"><b>[[Gene|Gene:]]</b></td><td class="sblockDat">ROBO2, KIAA1568 ([http://www.ncbi.nlm.nih.gov/Taxonomy/Browser/wwwtax.cgi?mode=Info&srchmode=5&id=9606 HUMAN])</td></tr>
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<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=6i9s FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=6i9s OCA], [http://pdbe.org/6i9s PDBe], [http://www.rcsb.org/pdb/explore.do?structureId=6i9s RCSB], [http://www.ebi.ac.uk/pdbsum/6i9s PDBsum], [http://prosat.h-its.org/prosat/prosatexe?pdbcode=6i9s ProSAT]</span></td></tr>
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</table>
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== Disease ==
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[[http://www.uniprot.org/uniprot/ROBO2_HUMAN ROBO2_HUMAN]] Defects in ROBO2 are the cause of vesicoureteral reflux type 2 (VUR2) [MIM:[http://omim.org/entry/610878 610878]]. VUR is a complex, genetically heterogeneous developmental disorder characterized by the retrograde flow of urine from the bladder into the ureter and is associated with reflux nephropathy, the cause of 15% of end-stage renal disease in children and young adults.<ref>PMID:17357069</ref> Note=A chromosomal aberration involving ROBO2 is a cause of multiple congenital abnormalities, including severe bilateral VUR with ureterovesical junction defects. Translocation t(Y;3)(p11;p12) with PCDH11Y. This translocation disrupts ROBO2 and produces dominant-negative ROBO2 proteins that abrogate SLIT-ROBO signaling in vitro.
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== Function ==
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[[http://www.uniprot.org/uniprot/ROBO2_HUMAN ROBO2_HUMAN]] Receptor for SLIT2, and probably SLIT1, which are thought to act as molecular guidance cue in cellular migration, including axonal navigation at the ventral midline of the neural tube and projection of axons to different regions during neuronal development.
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<div style="background-color:#fffaf0;">
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== Publication Abstract from PubMed ==
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Proper brain function requires high-precision neuronal expansion and wiring, processes controlled by the transmembrane Roundabout (Robo) receptor family and their Slit ligands. Despite their great importance, the molecular mechanism by which Robos' switch from "off" to "on" states remains unclear. Here, we report a 3.6 A crystal structure of the intact human Robo2 ectodomain (domains D1-8). We demonstrate that Robo cis dimerization via D4 is conserved through hRobo1, 2, and 3 and the C. elegans homolog SAX-3 and is essential for SAX-3 function in vivo. The structure reveals two levels of auto-inhibition that prevent premature activation: (1) cis blocking of the D4 dimerization interface and (2) trans interactions between opposing Robo receptors that fasten the D4-blocked conformation. Complementary experiments in mouse primary neurons and C. elegans support the auto-inhibition model. These results suggest that Slit stimulation primarily drives the release of Robo auto-inhibition required for dimerization and activation.
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Authors:
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Structural Principles in Robo Activation and Auto-inhibition.,Barak R, Yom-Tov G, Guez-Haddad J, Gasri-Plotnitsky L, Maimon R, Cohen-Berkman M, McCarthy AA, Perlson E, Henis-Korenblit S, Isupov MN, Opatowsky Y Cell. 2019 Mar 4. pii: S0092-8674(19)30153-9. doi: 10.1016/j.cell.2019.02.004. PMID:30853216<ref>PMID:30853216</ref>
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Description:
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From MEDLINE&reg;/PubMed&reg;, a database of the U.S. National Library of Medicine.<br>
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[[Category: Unreleased Structures]]
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</div>
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<div class="pdbe-citations 6i9s" style="background-color:#fffaf0;"></div>
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== References ==
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<references/>
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__TOC__
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</StructureSection>
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[[Category: Human]]
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[[Category: Large Structures]]
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[[Category: Barak, R]]
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[[Category: Isupov, N M]]
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[[Category: Opatowsky, Y]]
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[[Category: Axon guidance]]
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[[Category: Robo]]
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[[Category: Signaling protein]]
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[[Category: Slit]]

Current revision

hRobo2 Extracellular Domains 2-3

PDB ID 6i9s

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