2v5n: Difference between revisions

Revision as of 19:53, 21 February 2008

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 with as ligand. Known structural/functional Sites: and . 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 Feb 21 18:53:17 2008

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OCA

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 ==Overview==
-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.
 ==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 [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].
 ==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. 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://ispc.weizmann.ac.il//pmbin/getpm?pmid=18046459 18046459]
 [[Category: Homo sapiens]]
 [[Category: Single protein]]
-[[Category: Boxel, G.Van.]]
+[[Category: Boxel, G Van.]]
 [[Category: Brown, J.]]
 [[Category: Delaine, C.]]
 [[Category: Denley, A.]]
-[[Category: Forbes, B.E.]]
+[[Category: Forbes, B E.]]
-[[Category: Gilbert, R.J.]]
+[[Category: Gilbert, R J.]]
-[[Category: Hassan, A.B.]]
+[[Category: Hassan, A B.]]
-[[Category: Jones, E.Y.]]
+[[Category: Jones, E Y.]]
 [[Category: Siebold, C.]]
-[[Category: Wallace, J.C.]]
+[[Category: Wallace, J C.]]
-[[Category: Zaccheo, O.J.]]
+[[Category: Zaccheo, O J.]]
 [[Category: NAG]]
 [[Category: beta barrel]]
@@ Line 38: / Line 38: @@
 [[Category: transport]]
-''Page seeded by [http://oca.weizmann.ac.il/oca OCA ] on Wed Jan 23 11:46:17 2008''
+''Page seeded by [http://oca.weizmann.ac.il/oca OCA ] on Thu Feb 21 18:53:17 2008''