2v5n

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[[Image:2v5n.jpg|left|200px]]<br /><applet load="2v5n" size="350" color="white" frame="true" align="right" spinBox="true"
 
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caption="2v5n, resolution 3.20&Aring;" />
 
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'''STRUCTURE OF HUMAN IGF2R DOMAINS 11-12'''<br />
 
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==Overview==
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==STRUCTURE OF HUMAN IGF2R DOMAINS 11-12==
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<StructureSection load='2v5n' size='340' side='right'caption='[[2v5n]], [[Resolution|resolution]] 3.20&Aring;' scene=''>
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== Structural highlights ==
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<table><tr><td colspan='2'>[[2v5n]] is a 1 chain structure with sequence from [https://en.wikipedia.org/wiki/Human Human]. Full crystallographic information is available from [http://oca.weizmann.ac.il/oca-bin/ocashort?id=2V5N OCA]. For a <b>guided tour on the structure components</b> use [https://proteopedia.org/fgij/fg.htm?mol=2V5N FirstGlance]. <br>
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</td></tr><tr id='ligand'><td class="sblockLbl"><b>[[Ligand|Ligands:]]</b></td><td class="sblockDat" id="ligandDat"><scene name='pdbligand=NAG:N-ACETYL-D-GLUCOSAMINE'>NAG</scene></td></tr>
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<tr id='NonStdRes'><td class="sblockLbl"><b>[[Non-Standard_Residue|NonStd Res:]]</b></td><td class="sblockDat"><scene name='pdbligand=MSE:SELENOMETHIONINE'>MSE</scene></td></tr>
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<tr id='related'><td class="sblockLbl"><b>[[Related_structure|Related:]]</b></td><td class="sblockDat"><div style='overflow: auto; max-height: 3em;'>[[1e6f|1e6f]], [[1gp0|1gp0]], [[1gp3|1gp3]], [[1gqb|1gqb]], [[1jpl|1jpl]], [[1jwg|1jwg]], [[1lf8|1lf8]], [[2cnj|2cnj]], [[2v5o|2v5o]], [[2v5p|2v5p]]</div></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=2v5n FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=2v5n OCA], [https://pdbe.org/2v5n PDBe], [https://www.rcsb.org/pdb/explore.do?structureId=2v5n RCSB], [https://www.ebi.ac.uk/pdbsum/2v5n PDBsum], [https://prosat.h-its.org/prosat/prosatexe?pdbcode=2v5n 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/v5/2v5n_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=2v5n 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 ==
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.
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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2V5N 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> as [http://en.wikipedia.org/wiki/ligand ligand]. Known structural/functional Sites: <scene name='pdbsite=AC1:Nag+Binding+Site+For+Chain+A'>AC1</scene> and <scene name='pdbsite=AC2:Nag+Binding+Site+For+Chain+A'>AC2</scene>. Full crystallographic information is available from [http://oca.weizmann.ac.il/oca-bin/ocashort?id=2V5N 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. 2008 Jan 9;27(1):265-76. Epub 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 2v5n" 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: 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 Thu Feb 21 18:53:17 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: Human]]
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[[Category: Large Structures]]
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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: 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: Receptor]]
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[[Category: Transmembrane]]
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[[Category: Transport]]

Current revision

STRUCTURE OF HUMAN IGF2R DOMAINS 11-12

PDB ID 2v5n

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