2v5p

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{{STRUCTURE_2v5p| PDB=2v5p | SCENE= }}
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==COMPLEX STRUCTURE OF HUMAN IGF2R DOMAINS 11-13 BOUND TO IGF-II==
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===COMPLEX STRUCTURE OF HUMAN IGF2R DOMAINS 11-13 BOUND TO IGF-II===
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<StructureSection load='2v5p' size='340' side='right' caption='[[2v5p]], [[Resolution|resolution]] 4.10&Aring;' scene=''>
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{{ABSTRACT_PUBMED_18046459}}
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== Structural highlights ==
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<table><tr><td colspan='2'>[[2v5p]] is a 4 chain structure with sequence from [http://en.wikipedia.org/wiki/Homo_sapiens Homo sapiens]. Full crystallographic information is available from [http://oca.weizmann.ac.il/oca-bin/ocashort?id=2V5P OCA]. For a <b>guided tour on the structure components</b> use [http://oca.weizmann.ac.il/oca-docs/fgij/fg.htm?mol=2V5P FirstGlance]. <br>
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</td></tr><tr><td class="sblockLbl"><b>[[Ligand|Ligands:]]</b></td><td class="sblockDat"><scene name='pdbligand=BMA:BETA-D-MANNOSE'>BMA</scene>, <scene name='pdbligand=NAG:N-ACETYL-D-GLUCOSAMINE'>NAG</scene><br>
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<tr><td class="sblockLbl"><b>[[Related_structure|Related:]]</b></td><td class="sblockDat">[[1gf2|1gf2]], [[1igl|1igl]], [[1e6f|1e6f]], [[1gp0|1gp0]], [[1gp3|1gp3]], [[1gqb|1gqb]], [[1jpl|1jpl]], [[1jwg|1jwg]], [[1lf8|1lf8]], [[2cnj|2cnj]], [[2v5n|2v5n]], [[2v5o|2v5o]]</td></tr>
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<tr><td class="sblockLbl"><b>Resources:</b></td><td class="sblockDat"><span class='plainlinks'>[http://oca.weizmann.ac.il/oca-docs/fgij/fg.htm?mol=2v5p FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=2v5p OCA], [http://www.rcsb.org/pdb/explore.do?structureId=2v5p RCSB], [http://www.ebi.ac.uk/pdbsum/2v5p PDBsum]</span></td></tr>
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<table>
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== Disease ==
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[[http://www.uniprot.org/uniprot/IGF2_HUMAN IGF2_HUMAN]] Epigenetic changes of DNA hypomethylation in IGF2 are a cause of Silver-Russell syndrome (SRS) [MIM:[http://omim.org/entry/180860 180860]]. A clinically heterogeneous condition characterized by severe intrauterine growth retardation, poor postnatal growth, craniofacial features such as a triangular shaped face and a broad forehead, body asymmetry, and a variety of minor malformations. The phenotypic expression changes during childhood and adolescence, with the facial features and asymmetry usually becoming more subtle with age.<ref>PMID:19066168</ref>
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== Function ==
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[[http://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> [[http://www.uniprot.org/uniprot/IGF2_HUMAN IGF2_HUMAN]] The insulin-like growth factors possess growth-promoting activity. In vitro, they are potent mitogens for cultured cells. IGF-II is influenced by placental lactogen and may play a role in fetal development.<ref>PMID:16912056</ref> Preptin undergoes glucose-mediated co-secretion with insulin, and acts as physiological amplifier of glucose-mediated insulin secretion. Exhibits osteogenic properties by increasing osteoblast mitogenic activity through phosphoactivation of MAPK1 and MAPK3.<ref>PMID:16912056</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/v5/2v5p_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/chain_selection.php?pdb_ID=2ata 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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==Disease==
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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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[[http://www.uniprot.org/uniprot/IGF2_HUMAN IGF2_HUMAN]] Epigenetic changes of DNA hypomethylation in IGF2 are a cause of Silver-Russell syndrome (SRS) [MIM:[http://omim.org/entry/180860 180860]]. A clinically heterogeneous condition characterized by severe intrauterine growth retardation, poor postnatal growth, craniofacial features such as a triangular shaped face and a broad forehead, body asymmetry, and a variety of minor malformations. The phenotypic expression changes during childhood and adolescence, with the facial features and asymmetry usually becoming more subtle with age.<ref>PMID:19066168</ref>
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==Function==
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From MEDLINE&reg;/PubMed&reg;, a database of the U.S. National Library of Medicine.<br>
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[[http://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> [[http://www.uniprot.org/uniprot/IGF2_HUMAN IGF2_HUMAN]] The insulin-like growth factors possess growth-promoting activity. In vitro, they are potent mitogens for cultured cells. IGF-II is influenced by placental lactogen and may play a role in fetal development.<ref>PMID:16912056</ref> Preptin undergoes glucose-mediated co-secretion with insulin, and acts as physiological amplifier of glucose-mediated insulin secretion. Exhibits osteogenic properties by increasing osteoblast mitogenic activity through phosphoactivation of MAPK1 and MAPK3.<ref>PMID:16912056</ref>
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</div>
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==About this Structure==
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[[2v5p]] is a 4 chain structure with sequence from [http://en.wikipedia.org/wiki/Homo_sapiens Homo sapiens]. Full crystallographic information is available from [http://oca.weizmann.ac.il/oca-bin/ocashort?id=2V5P OCA].
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==See Also==
==See Also==
*[[Insulin-like growth factor receptor|Insulin-like growth factor receptor]]
*[[Insulin-like growth factor receptor|Insulin-like growth factor receptor]]
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== References ==
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==Reference==
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<references/>
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<ref group="xtra">PMID:018046459</ref><references group="xtra"/><references/>
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__TOC__
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</StructureSection>
[[Category: Homo sapiens]]
[[Category: Homo sapiens]]
[[Category: Boxel, G Van.]]
[[Category: Boxel, G Van.]]

Revision as of 02:04, 1 October 2014

COMPLEX STRUCTURE OF HUMAN IGF2R DOMAINS 11-13 BOUND TO IGF-II

2v5p, resolution 4.10Å

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