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2v5o

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(New page: 200px<br /><applet load="2v5o" size="350" color="white" frame="true" align="right" spinBox="true" caption="2v5o, resolution 2.91&Aring;" /> '''STRUCTURE OF HUMAN I...)
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[[Image:2v5o.jpg|left|200px]]<br /><applet load="2v5o" size="350" color="white" frame="true" align="right" spinBox="true"
 
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caption="2v5o, resolution 2.91&Aring;" />
 
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'''STRUCTURE OF HUMAN IGF2R DOMAINS 11-14'''<br />
 
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==Overview==
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==STRUCTURE OF HUMAN IGF2R DOMAINS 11-14==
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Embryonic development and normal growth require exquisite control of, insulin-like growth factors (IGFs). In mammals the extracellular region of, the cation-independent mannose-6-phosphate receptor has gained an, IGF-II-binding function and is termed type II IGF receptor (IGF2R). IGF2R, sequesters IGF-II; imbalances occur in cancers and IGF2R is implicated in, tumour suppression. We report crystal structures of IGF2R domains 11-12, 11-12-13-14 and domains 11-12-13/IGF-II complex. A distinctive, juxtaposition of these domains provides the IGF-II-binding unit, with, domain 11 directly interacting with IGF-II and domain 13 modulating, binding site flexibility. Our complex shows that Phe19 and Leu53 of IGF-II, lock into a hydrophobic pocket unique to domain 11 of mammalian IGF2Rs., Mutagenesis analyses confirm this IGF-II 'binding-hotspot', revealing that, IGF-binding proteins and IGF2R have converged on the same high-affinity, site.
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<StructureSection load='2v5o' size='340' side='right'caption='[[2v5o]], [[Resolution|resolution]] 2.91&Aring;' scene=''>
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== Structural highlights ==
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<table><tr><td colspan='2'>[[2v5o]] is a 1 chain structure with sequence from [https://en.wikipedia.org/wiki/Homo_sapiens Homo sapiens]. Full crystallographic information is available from [http://oca.weizmann.ac.il/oca-bin/ocashort?id=2V5O OCA]. For a <b>guided tour on the structure components</b> use [https://proteopedia.org/fgij/fg.htm?mol=2V5O FirstGlance]. <br>
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</td></tr><tr id='method'><td class="sblockLbl"><b>[[Empirical_models|Method:]]</b></td><td class="sblockDat" id="methodDat">X-ray diffraction, [[Resolution|Resolution]] 2.91&#8491;</td></tr>
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<tr id='ligand'><td class="sblockLbl"><b>[[Ligand|Ligands:]]</b></td><td class="sblockDat" id="ligandDat"><scene name='pdbligand=CL:CHLORIDE+ION'>CL</scene>, <scene name='pdbligand=NAG:N-ACETYL-D-GLUCOSAMINE'>NAG</scene></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=2v5o FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=2v5o OCA], [https://pdbe.org/2v5o PDBe], [https://www.rcsb.org/pdb/explore.do?structureId=2v5o RCSB], [https://www.ebi.ac.uk/pdbsum/2v5o PDBsum], [https://prosat.h-its.org/prosat/prosatexe?pdbcode=2v5o ProSAT]</span></td></tr>
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</table>
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== Function ==
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[https://www.uniprot.org/uniprot/MPRI_HUMAN MPRI_HUMAN] Transport of phosphorylated lysosomal enzymes from the Golgi complex and the cell surface to lysosomes. Lysosomal enzymes bearing phosphomannosyl residues bind specifically to mannose-6-phosphate receptors in the Golgi apparatus and the resulting receptor-ligand complex is transported to an acidic prelyosomal compartment where the low pH mediates the dissociation of the complex. This receptor also binds IGF2. Acts as a positive regulator of T-cell coactivation, by binding DPP4.<ref>PMID:10900005</ref>
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== Evolutionary Conservation ==
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[[Image:Consurf_key_small.gif|200px|right]]
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Check<jmol>
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<jmolCheckbox>
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<scriptWhenChecked>; select protein; define ~consurf_to_do selected; consurf_initial_scene = true; script "/wiki/ConSurf/v5/2v5o_consurf.spt"</scriptWhenChecked>
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<scriptWhenUnchecked>script /wiki/extensions/Proteopedia/spt/initialview01.spt</scriptWhenUnchecked>
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<text>to colour the structure by Evolutionary Conservation</text>
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</jmolCheckbox>
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</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=2v5o ConSurf].
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<div style="clear:both"></div>
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<div style="background-color:#fffaf0;">
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== Publication Abstract from PubMed ==
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Embryonic development and normal growth require exquisite control of insulin-like growth factors (IGFs). In mammals the extracellular region of the cation-independent mannose-6-phosphate receptor has gained an IGF-II-binding function and is termed type II IGF receptor (IGF2R). IGF2R sequesters IGF-II; imbalances occur in cancers and IGF2R is implicated in tumour suppression. We report crystal structures of IGF2R domains 11-12, 11-12-13-14 and domains 11-12-13/IGF-II complex. A distinctive juxtaposition of these domains provides the IGF-II-binding unit, with domain 11 directly interacting with IGF-II and domain 13 modulating binding site flexibility. Our complex shows that Phe19 and Leu53 of IGF-II lock into a hydrophobic pocket unique to domain 11 of mammalian IGF2Rs. Mutagenesis analyses confirm this IGF-II 'binding-hotspot', revealing that IGF-binding proteins and IGF2R have converged on the same high-affinity site.
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==About this Structure==
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Structure and functional analysis of the IGF-II/IGF2R interaction.,Brown J, Delaine C, Zaccheo OJ, Siebold C, Gilbert RJ, van Boxel G, Denley A, Wallace JC, Hassan AB, Forbes BE, Jones EY EMBO J. 2008 Jan 9;27(1):265-76. Epub 2007 Nov 29. PMID:18046459<ref>PMID:18046459</ref>
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2V5O is a [http://en.wikipedia.org/wiki/Single_protein Single protein] structure of sequence from [http://en.wikipedia.org/wiki/Homo_sapiens Homo sapiens] with <scene name='pdbligand=NAG:'>NAG</scene> and <scene name='pdbligand=CL:'>CL</scene> as [http://en.wikipedia.org/wiki/ligands ligands]. Known structural/functional Sites: <scene name='pdbsite=AC1:Nag Binding Site For Chain A'>AC1</scene>, <scene name='pdbsite=AC2:Nag Binding Site For Chain A'>AC2</scene>, <scene name='pdbsite=AC3:Nag Binding Site For Chain A'>AC3</scene>, <scene name='pdbsite=AC4:Cl Binding Site For Chain A'>AC4</scene> and <scene name='pdbsite=AC5:Cl Binding Site For Chain A'>AC5</scene>. Full crystallographic information is available from [http://oca.weizmann.ac.il/oca-bin/ocashort?id=2V5O OCA].
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==Reference==
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From MEDLINE&reg;/PubMed&reg;, a database of the U.S. National Library of Medicine.<br>
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Structure and functional analysis of the IGF-II/IGF2R interaction., Brown J, Delaine C, Zaccheo OJ, Siebold C, Gilbert RJ, van Boxel G, Denley A, Wallace JC, Hassan AB, Forbes BE, Jones EY, EMBO J. 2007 Nov 29;. PMID:[http://ispc.weizmann.ac.il//pmbin/getpm?pmid=18046459 18046459]
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</div>
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[[Category: Homo sapiens]]
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<div class="pdbe-citations 2v5o" style="background-color:#fffaf0;"></div>
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[[Category: Single protein]]
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[[Category: Boxel, G.Van.]]
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[[Category: Brown, J.]]
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[[Category: Delaine, C.]]
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[[Category: Denley, A.]]
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[[Category: Forbes, B.E.]]
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[[Category: Gilbert, R.J.]]
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[[Category: Hassan, A.B.]]
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[[Category: Jones, E.Y.]]
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[[Category: Siebold, C.]]
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[[Category: Wallace, J.C.]]
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[[Category: Zaccheo, O.J.]]
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[[Category: CL]]
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[[Category: NAG]]
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[[Category: beta barrel]]
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[[Category: cation independent mannose 6-phosphate]]
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[[Category: fibronectin type ii]]
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[[Category: glycoprotein]]
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[[Category: insulin-like growth factor]]
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[[Category: lysosome]]
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[[Category: membrane]]
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[[Category: phosphorylation]]
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[[Category: polymorphism]]
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[[Category: receptor]]
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[[Category: transmembrane]]
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[[Category: transport]]
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''Page seeded by [http://oca.weizmann.ac.il/oca OCA ] on Wed Jan 23 11:46:20 2008''
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==See Also==
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*[[Insulin-like growth factor receptor|Insulin-like growth factor receptor]]
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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: Homo sapiens]]
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[[Category: Large Structures]]
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[[Category: Brown J]]
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[[Category: Delaine C]]
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[[Category: Denley A]]
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[[Category: Forbes BE]]
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[[Category: Gilbert RJ]]
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[[Category: Hassan AB]]
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[[Category: Jones EY]]
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[[Category: Siebold C]]
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[[Category: Wallace JC]]
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[[Category: Zaccheo OJ]]
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[[Category: Van Boxel G]]

Current revision

STRUCTURE OF HUMAN IGF2R DOMAINS 11-14

PDB ID 2v5o

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