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2v5p

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Revision as of 06:57, 28 February 2018

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

Structural highlights

2v5p is a 4 chain structure with sequence from Human. Full crystallographic information is available from OCA. For a guided tour on the structure components use FirstGlance.
Ligands:	,
Related:	1gf2, 1igl, 1e6f, 1gp0, 1gp3, 1gqb, 1jpl, 1jwg, 1lf8, 2cnj, 2v5n, 2v5o
Resources:	FirstGlance, OCA, PDBe, RCSB, PDBsum, ProSAT

Disease

[IGF2_HUMAN] Epigenetic changes of DNA hypomethylation in IGF2 are a cause of Silver-Russell syndrome (SRS) [MIM: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.^[1]

Function

[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.^[2] [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.^[3] 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.^[4]

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

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.

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^[5]

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

References

↑ Bartholdi D, Krajewska-Walasek M, Ounap K, Gaspar H, Chrzanowska KH, Ilyana H, Kayserili H, Lurie IW, Schinzel A, Baumer A. Epigenetic mutations of the imprinted IGF2-H19 domain in Silver-Russell syndrome (SRS): results from a large cohort of patients with SRS and SRS-like phenotypes. J Med Genet. 2009 Mar;46(3):192-7. doi: 10.1136/jmg.2008.061820. Epub 2008 Dec 9. PMID:19066168 doi:10.1136/jmg.2008.061820
↑ Ikushima H, Munakata Y, Ishii T, Iwata S, Terashima M, Tanaka H, Schlossman SF, Morimoto C. Internalization of CD26 by mannose 6-phosphate/insulin-like growth factor II receptor contributes to T cell activation. Proc Natl Acad Sci U S A. 2000 Jul 18;97(15):8439-44. PMID:10900005
↑ Cornish J, Callon KE, Bava U, Watson M, Xu X, Lin JM, Chan VA, Grey AB, Naot D, Buchanan CM, Cooper GJ, Reid IR. Preptin, another peptide product of the pancreatic beta-cell, is osteogenic in vitro and in vivo. Am J Physiol Endocrinol Metab. 2007 Jan;292(1):E117-22. Epub 2006 Aug 15. PMID:16912056 doi:10.1152/ajpendo.00642.2005
↑ Cornish J, Callon KE, Bava U, Watson M, Xu X, Lin JM, Chan VA, Grey AB, Naot D, Buchanan CM, Cooper GJ, Reid IR. Preptin, another peptide product of the pancreatic beta-cell, is osteogenic in vitro and in vivo. Am J Physiol Endocrinol Metab. 2007 Jan;292(1):E117-22. Epub 2006 Aug 15. PMID:16912056 doi:10.1152/ajpendo.00642.2005
↑ Brown J, Delaine C, Zaccheo OJ, Siebold C, Gilbert RJ, van Boxel G, Denley A, Wallace JC, Hassan AB, Forbes BE, Jones EY. Structure and functional analysis of the IGF-II/IGF2R interaction. EMBO J. 2008 Jan 9;27(1):265-76. Epub 2007 Nov 29. PMID:18046459

1 Structural highlights
2 Disease
3 Function
4 Evolutionary Conservation
5 Publication Abstract from PubMed
6 References

Proteopedia Page Contributors and Editors (what is this?)

OCA

Retrieved from "http://52.214.119.220/wiki/index.php/2v5p"

@@ Line 1: / Line 1: @@
 ==COMPLEX STRUCTURE OF HUMAN IGF2R DOMAINS 11-13 BOUND TO IGF-II==
 <StructureSection load='2v5p' size='340' side='right' caption='[[2v5p]], [[Resolution|resolution]] 4.10&Aring;' scene=''>
@@ Line 5: / Line 6: @@
 </td></tr><tr id='ligand'><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></td></tr>
 <tr id='related'><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>
-<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=2v5p FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=2v5p OCA], [http://pdbe.org/2v5p PDBe], [http://www.rcsb.org/pdb/explore.do?structureId=2v5p RCSB], [http://www.ebi.ac.uk/pdbsum/2v5p PDBsum]</span></td></tr>
+<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=2v5p FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=2v5p OCA], [http://pdbe.org/2v5p PDBe], [http://www.rcsb.org/pdb/explore.do?structureId=2v5p RCSB], [http://www.ebi.ac.uk/pdbsum/2v5p PDBsum], [http://prosat.h-its.org/prosat/prosatexe?pdbcode=2v5p ProSAT]</span></td></tr>
 </table>
 == Disease ==
@@ Line 15: / Line 16: @@
 Check<jmol>
   <jmolCheckbox>
-    <scriptWhenChecked>select protein; define ~consurf_to_do selected; consurf_initial_scene = true; script "/wiki/ConSurf/v5/2v5p_consurf.spt"</scriptWhenChecked>
+    <scriptWhenChecked>; select protein; define ~consurf_to_do selected; consurf_initial_scene = true; script "/wiki/ConSurf/v5/2v5p_consurf.spt"</scriptWhenChecked>
     <scriptWhenUnchecked>script /wiki/extensions/Proteopedia/spt/initialview01.spt</scriptWhenUnchecked>
     <text>to colour the structure by Evolutionary Conservation</text>
@@ Line 30: / Line 31: @@
 </div>
 <div class="pdbe-citations 2v5p" style="background-color:#fffaf0;"></div>
-==See Also==
-*[[Insulin-like growth factor receptor|Insulin-like growth factor receptor]]
 == References ==
 <references/>
@@ Line 38: / Line 36: @@
 </StructureSection>
 [[Category: Human]]
-[[Category: Boxel, G Van]]
+[[Category: Boxel, G van]]
 [[Category: Brown, J]]
 [[Category: Delaine, C]]
@@ Line 57: / Line 55: @@
 [[Category: Membrane]]
 [[Category: Phosphorylation]]
+[[Category: Polymorphism]]
 [[Category: Receptor]]
 [[Category: Receptor-glycoprotein complex]]

2v5p

From Proteopedia

Revision as of 06:57, 28 February 2018

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

Structural highlights

Disease

Function

Evolutionary Conservation

Publication Abstract from PubMed

References

Contents

Proteopedia Page Contributors and Editors (what is this?)

Views

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