2vr9: Difference between revisions

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==Drosophila Robo IG1-2 (tetragonal form)==
The line below this paragraph, containing "STRUCTURE_2vr9", creates the "Structure Box" on the page.
<StructureSection load='2vr9' size='340' side='right'caption='[[2vr9]], [[Resolution|resolution]] 3.20&Aring;' scene=''>
You may change the PDB parameter (which sets the PDB file loaded into the applet)
== Structural highlights ==
or the SCENE parameter (which sets the initial scene displayed when the page is loaded),
<table><tr><td colspan='2'>[[2vr9]] 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=2VR9 OCA]. For a <b>guided tour on the structure components</b> use [https://proteopedia.org/fgij/fg.htm?mol=2VR9 FirstGlance]. <br>
or leave the SCENE parameter empty for the default display.
</td></tr><tr id='method'><td class="sblockLbl"><b>[[Empirical_models|Method:]]</b></td><td class="sblockDat" id="methodDat">X-ray diffraction, [[Resolution|Resolution]] 3.2&#8491;</td></tr>
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<tr id='resources'><td class="sblockLbl"><b>Resources:</b></td><td class="sblockDat"><span class='plainlinks'>[https://proteopedia.org/fgij/fg.htm?mol=2vr9 FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=2vr9 OCA], [https://pdbe.org/2vr9 PDBe], [https://www.rcsb.org/pdb/explore.do?structureId=2vr9 RCSB], [https://www.ebi.ac.uk/pdbsum/2vr9 PDBsum], [https://prosat.h-its.org/prosat/prosatexe?pdbcode=2vr9 ProSAT]</span></td></tr>
{{STRUCTURE_2vr9|  PDB=2vr9  |  SCENE=  }}
</table>
== Function ==
[https://www.uniprot.org/uniprot/O44924_DROME O44924_DROME]
== 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/vr/2vr9_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=2vr9 ConSurf].
<div style="clear:both"></div>
<div style="background-color:#fffaf0;">
== Publication Abstract from PubMed ==
Recognition of the secreted protein Slit by transmembrane receptors of the Robo family provides important signals in the development of the nervous system and other organs, as well as in tumor metastasis and angiogenesis. Heparan sulfate (HS) proteoglycans serve as essential co-receptors in Slit-Robo signaling. Previous studies have shown that the second leucinerich repeat domain of Slit, D2, binds to the N-terminal immunoglobulin-like domains of Robo, IG1-2. Here we present two crystal structures of Drosophila Robo IG1-2, one of which contains a bound heparin-derived oligosaccharide. Using structure-based mutagenesis of a Robo IG1-5 construct we identified key Slit binding residues (Thr-74, Phe-114, Arg-117) forming a conserved patch on the surface of IG1; mutation of similarly conserved residues in IG2 had no effect on Slit binding. Mutation of conserved basic residues in IG1 (Lys-69, Arg-117, Lys-122, Lys-123), but not in IG2, reduced binding of Robo IG1-5 to heparin, in full agreement with the Robo-heparin co-crystal structure. Our collective results, together with a recent crystal structure of a minimal human Slit-Robo complex ( Morlot, C., Thielens, N. M., Ravelli, R. B., Hemrika, W., Romijn, R. A., Gros, P., Cusack, S., and McCarthy, A. A. (2007) Proc. Natl. Acad. Sci. U.S.A. 104, 14923-14928 ), reveal a contiguous HS/heparin binding surface extending across the Slit-Robo interface. Based on the size of this composite binding site, we predict that at least five HS disaccharide units are required to support Slit-Robo signaling.


'''DROSOPHILA ROBO IG1-2 (TETRAGONAL FORM)'''
Structural and functional analysis of slit and heparin binding to immunoglobulin-like domains 1 and 2 of Drosophila Robo.,Fukuhara N, Howitt JA, Hussain SA, Hohenester E J Biol Chem. 2008 Jun 6;283(23):16226-34. Epub 2008 Mar 20. PMID:18359766<ref>PMID:18359766</ref>


 
From MEDLINE&reg;/PubMed&reg;, a database of the U.S. National Library of Medicine.<br>
==Overview==
</div>
Recognition of the secreted protein Slit by transmembrane receptors of the Robo family provides important signals in the development of the nervous system and other organs, as well as in tumour metastasis and angiogenesis. Heparan sulphate (HS) proteoglycans serve as essential co-receptors in Slit-Robo signalling. Previous studies have shown that the second leucine-rich repeat domain of Slit, D2, binds to the N-terminal immunoglobulin-like domains of Robo, IG1-2. Here we present two crystal structures of Drosophila Robo IG1-2, one of which contains a bound heparin-derived oligosaccharide. Using structure-based mutagenesis of a Robo IG1-5 construct we identified key Slit binding residues (Thr74, Phe114, Arg117) forming a conserved patch on the surface of IG1; mutation of similarly conserved residues in IG2 had no effect on Slit binding. Mutation of conserved basic residues in IG1 (Lys69, Arg117, Lys122, Lys123), but not in IG2, reduced binding of Robo IG1-5 to heparin, in full agreement with the Robo-heparin co-crystal structure. Our collective results, together with a recent crystal structure of a minimal human Slit-Robo complex (Morlot, C., Thielens, N. M., Ravelli, R. B., Hemrika, W., Romijn, R. A., Gros, P., Cusack, S., and McCarthy, A. A. (2007) Proc. Natl. Acad. Sci. U.S.A. 104, 14923-14928), reveal a contiguous HS/heparin binding surface extending across the Slit-Robo interface. Based on the size of this composite binding site, we predict that at least five HS disaccharide units are required to support Slit-Robo signalling.
<div class="pdbe-citations 2vr9" style="background-color:#fffaf0;"></div>
 
== References ==
==About this Structure==
<references/>
2VR9 is a [[Single protein]] structure of 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=2VR9 OCA].
__TOC__
 
</StructureSection>
==Reference==
Structural and functional analysis of Slit and heparin binding to immunoglobulin-like domains 1 and 2 of Drosophila Robo., Fukuhara N, Howitt JA, Hussain SA, Hohenester E, J Biol Chem. 2008 Mar 20;. PMID:[http://www.ncbi.nlm.nih.gov/pubmed/18359766 18359766]
[[Category: Drosophila melanogaster]]
[[Category: Drosophila melanogaster]]
[[Category: Single protein]]
[[Category: Large Structures]]
[[Category: Fukuhara, N.]]
[[Category: Fukuhara N]]
[[Category: Hohenester, E.]]
[[Category: Hohenester E]]
[[Category: Howitt, J A.]]
[[Category: Howitt JA]]
[[Category: Hussain, S.]]
[[Category: Hussain S]]
[[Category: Axon guidance]]
[[Category: Cell adhesion]]
[[Category: Immunoglobulin domain]]
[[Category: Immunoglobulin-like domain]]

Latest revision as of 08:32, 17 October 2024

Drosophila Robo IG1-2 (tetragonal form)Drosophila Robo IG1-2 (tetragonal form)

Structural highlights

2vr9 is a 3 chain structure with sequence from Drosophila melanogaster. Full crystallographic information is available from OCA. For a guided tour on the structure components use FirstGlance.
Method:X-ray diffraction, Resolution 3.2Å
Resources:FirstGlance, OCA, PDBe, RCSB, PDBsum, ProSAT

Function

O44924_DROME

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

Recognition of the secreted protein Slit by transmembrane receptors of the Robo family provides important signals in the development of the nervous system and other organs, as well as in tumor metastasis and angiogenesis. Heparan sulfate (HS) proteoglycans serve as essential co-receptors in Slit-Robo signaling. Previous studies have shown that the second leucinerich repeat domain of Slit, D2, binds to the N-terminal immunoglobulin-like domains of Robo, IG1-2. Here we present two crystal structures of Drosophila Robo IG1-2, one of which contains a bound heparin-derived oligosaccharide. Using structure-based mutagenesis of a Robo IG1-5 construct we identified key Slit binding residues (Thr-74, Phe-114, Arg-117) forming a conserved patch on the surface of IG1; mutation of similarly conserved residues in IG2 had no effect on Slit binding. Mutation of conserved basic residues in IG1 (Lys-69, Arg-117, Lys-122, Lys-123), but not in IG2, reduced binding of Robo IG1-5 to heparin, in full agreement with the Robo-heparin co-crystal structure. Our collective results, together with a recent crystal structure of a minimal human Slit-Robo complex ( Morlot, C., Thielens, N. M., Ravelli, R. B., Hemrika, W., Romijn, R. A., Gros, P., Cusack, S., and McCarthy, A. A. (2007) Proc. Natl. Acad. Sci. U.S.A. 104, 14923-14928 ), reveal a contiguous HS/heparin binding surface extending across the Slit-Robo interface. Based on the size of this composite binding site, we predict that at least five HS disaccharide units are required to support Slit-Robo signaling.

Structural and functional analysis of slit and heparin binding to immunoglobulin-like domains 1 and 2 of Drosophila Robo.,Fukuhara N, Howitt JA, Hussain SA, Hohenester E J Biol Chem. 2008 Jun 6;283(23):16226-34. Epub 2008 Mar 20. PMID:18359766[1]

From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine.

References

  1. ↑ Fukuhara N, Howitt JA, Hussain SA, Hohenester E. Structural and functional analysis of slit and heparin binding to immunoglobulin-like domains 1 and 2 of Drosophila Robo. J Biol Chem. 2008 Jun 6;283(23):16226-34. Epub 2008 Mar 20. PMID:18359766 doi:10.1074/jbc.M800688200

2vr9, resolution 3.20Å

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