2v5n: Difference between revisions

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[[Image:2v5n.jpg|left|200px]]


{{Structure
==STRUCTURE OF HUMAN IGF2R DOMAINS 11-12==
|PDB= 2v5n |SIZE=350|CAPTION= <scene name='initialview01'>2v5n</scene>, resolution 3.20&Aring;
<StructureSection load='2v5n' size='340' side='right'caption='[[2v5n]], [[Resolution|resolution]] 3.20&Aring;' scene=''>
|SITE= <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>
== Structural highlights ==
|LIGAND= <scene name='pdbligand=NAG:N-ACETYL-D-GLUCOSAMINE'>NAG</scene>
<table><tr><td colspan='2'>[[2v5n]] 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=2V5N OCA]. For a <b>guided tour on the structure components</b> use [https://proteopedia.org/fgij/fg.htm?mol=2V5N FirstGlance]. <br>
|ACTIVITY=  
</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>
|GENE=  
<tr id='ligand'><td class="sblockLbl"><b>[[Ligand|Ligands:]]</b></td><td class="sblockDat" id="ligandDat"><scene name='pdbligand=MSE:SELENOMETHIONINE'>MSE</scene>, <scene name='pdbligand=NAG:N-ACETYL-D-GLUCOSAMINE'>NAG</scene></td></tr>
}}
<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>
</table>
== Function ==
[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>
== 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/v5/2v5n_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=2v5n ConSurf].
<div style="clear:both"></div>
<div style="background-color:#fffaf0;">
== 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 OF HUMAN IGF2R DOMAINS 11-12'''
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>


From MEDLINE&reg;/PubMed&reg;, a database of the U.S. National Library of Medicine.<br>
</div>
<div class="pdbe-citations 2v5n" style="background-color:#fffaf0;"></div>


==Overview==
==See Also==
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.
*[[Insulin-like growth factor receptor|Insulin-like growth factor receptor]]
 
== References ==
==About this Structure==
<references/>
2V5N is a [[Single protein]] structure of 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=2V5N OCA].
__TOC__
 
</StructureSection>
==Reference==
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://www.ncbi.nlm.nih.gov/pubmed/18046459 18046459]
[[Category: Homo sapiens]]
[[Category: Homo sapiens]]
[[Category: Single protein]]
[[Category: Large Structures]]
[[Category: Boxel, G Van.]]
[[Category: Brown J]]
[[Category: Brown, J.]]
[[Category: Delaine C]]
[[Category: Delaine, C.]]
[[Category: Denley A]]
[[Category: Denley, A.]]
[[Category: Forbes BE]]
[[Category: Forbes, B E.]]
[[Category: Gilbert RJ]]
[[Category: Gilbert, R J.]]
[[Category: Hassan AB]]
[[Category: Hassan, A B.]]
[[Category: Jones EY]]
[[Category: Jones, E Y.]]
[[Category: Siebold C]]
[[Category: Siebold, C.]]
[[Category: Wallace JC]]
[[Category: Wallace, J C.]]
[[Category: Zaccheo OJ]]
[[Category: Zaccheo, O J.]]
[[Category: Van Boxel G]]
[[Category: NAG]]
[[Category: beta barrel]]
[[Category: cation independent mannose 6-phosphate]]
[[Category: fibronectin type ii]]
[[Category: glycoprotein]]
[[Category: insulin-like growth factor]]
[[Category: lysosome]]
[[Category: membrane]]
[[Category: phosphorylation]]
[[Category: polymorphism]]
[[Category: receptor]]
[[Category: transmembrane]]
[[Category: transport]]
 
''Page seeded by [http://oca.weizmann.ac.il/oca OCA ] on Thu Mar 20 18:43:18 2008''

Latest revision as of 04:26, 21 November 2024

STRUCTURE OF HUMAN IGF2R DOMAINS 11-12STRUCTURE OF HUMAN IGF2R DOMAINS 11-12

Structural highlights

2v5n is a 1 chain structure with sequence from Homo sapiens. Full crystallographic information is available from OCA. For a guided tour on the structure components use FirstGlance.
Method:X-ray diffraction, Resolution 3.2Å
Ligands:,
Resources:FirstGlance, OCA, PDBe, RCSB, PDBsum, ProSAT

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.[1]

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[2]

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

See Also

References

  1. ↑ 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
  2. ↑ 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

2v5n, resolution 3.20Å

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