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STRUCTURE OF HUMAN IGF2R DOMAINS 11-12

OverviewOverview

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.

About this StructureAbout this Structure

2V5N is a Single protein structure of sequence from Homo sapiens. Full crystallographic information is available from OCA.

ReferenceReference

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

Page seeded by OCA on Thu Mar 20 18:43:18 2008

Proteopedia Page Contributors and Editors (what is this?)Proteopedia Page Contributors and Editors (what is this?)

OCA

@@ Line 1: / Line 1: @@
-[[Image:2v5n.jpg|left|200px]]<br /><applet load="2v5n" size="350" color="white" frame="true" align="right" spinBox="true"
+[[Image:2v5n.jpg|left|200px]]
-caption="2v5n, resolution 3.20&Aring;" />
-'''STRUCTURE OF HUMAN IGF2R DOMAINS 11-12'''<br />
+ {{Structure
+|PDB= 2v5n |SIZE=350|CAPTION= <scene name='initialview01'>2v5n</scene>, resolution 3.20&Aring;
+|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>
+|LIGAND= <scene name='pdbligand=NAG:N-ACETYL-D-GLUCOSAMINE'>NAG</scene>
+|ACTIVITY=
+|GENE=
+}}
+'''STRUCTURE OF HUMAN IGF2R DOMAINS 11-12'''
 ==Overview==
@@ Line 7: / Line 16: @@
 ==About this Structure==
-V5N 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].
+V5N 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].
 ==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://ispc.weizmann.ac.il//pmbin/getpm?pmid=18046459 18046459]
+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: Single protein]]
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 [[Category: transport]]
-''Page seeded by [http://oca.weizmann.ac.il/oca OCA ] on Thu Feb 21 18:53:17 2008''
+''Page seeded by [http://oca.weizmann.ac.il/oca OCA ] on Thu Mar 20 18:43:18 2008''