2v5p
From Proteopedia
(New page: 200px<br /><applet load="2v5p" size="350" color="white" frame="true" align="right" spinBox="true" caption="2v5p, resolution 4.10Å" /> '''COMPLEX STRUCTURE OF...) |
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==Overview== | ==Overview== | ||
| - | Embryonic development and normal growth require exquisite control of | + | 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== | ==About this Structure== | ||
| - | 2V5P is a [http://en.wikipedia.org/wiki/Protein_complex Protein complex] structure of sequences 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>, <scene name='pdbsite=AC2:Nag Binding Site For Chain A'>AC2</scene>, <scene name='pdbsite=AC3:Nag Binding Site For Chain A'>AC3</scene>, <scene name='pdbsite=AC5:Bma Binding Site For Chain A'>AC5</scene>, <scene name='pdbsite=AC6:Nag Binding Site For Chain B'>AC6</scene>, <scene name='pdbsite=AC7:Nag Binding Site For Chain B'>AC7</scene> and <scene name='pdbsite=AC8:Bma Binding Site For Chain A'>AC8</scene>. Full crystallographic information is available from [http://oca.weizmann.ac.il/oca-bin/ocashort?id=2V5P OCA]. | + | 2V5P is a [http://en.wikipedia.org/wiki/Protein_complex Protein complex] structure of sequences 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>, <scene name='pdbsite=AC2:Nag+Binding+Site+For+Chain+A'>AC2</scene>, <scene name='pdbsite=AC3:Nag+Binding+Site+For+Chain+A'>AC3</scene>, <scene name='pdbsite=AC5:Bma+Binding+Site+For+Chain+A'>AC5</scene>, <scene name='pdbsite=AC6:Nag+Binding+Site+For+Chain+B'>AC6</scene>, <scene name='pdbsite=AC7:Nag+Binding+Site+For+Chain+B'>AC7</scene> and <scene name='pdbsite=AC8:Bma+Binding+Site+For+Chain+A'>AC8</scene>. Full crystallographic information is available from [http://oca.weizmann.ac.il/oca-bin/ocashort?id=2V5P OCA]. |
==Reference== | ==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 | + | 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: Homo sapiens]] | ||
[[Category: Protein complex]] | [[Category: Protein complex]] | ||
| - | [[Category: Boxel, G | + | [[Category: Boxel, G Van.]] |
[[Category: Brown, J.]] | [[Category: Brown, J.]] | ||
[[Category: Delaine, C.]] | [[Category: Delaine, C.]] | ||
[[Category: Denley, A.]] | [[Category: Denley, A.]] | ||
| - | [[Category: Forbes, B | + | [[Category: Forbes, B E.]] |
| - | [[Category: Gilbert, R | + | [[Category: Gilbert, R J.]] |
| - | [[Category: Hassan, A | + | [[Category: Hassan, A B.]] |
| - | [[Category: Jones, E | + | [[Category: Jones, E Y.]] |
[[Category: Siebold, C.]] | [[Category: Siebold, C.]] | ||
| - | [[Category: Wallace, J | + | [[Category: Wallace, J C.]] |
| - | [[Category: Zaccheo, O | + | [[Category: Zaccheo, O J.]] |
[[Category: NAG]] | [[Category: NAG]] | ||
[[Category: beta barrel]] | [[Category: beta barrel]] | ||
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[[Category: transport]] | [[Category: transport]] | ||
| - | ''Page seeded by [http://oca.weizmann.ac.il/oca OCA ] on | + | ''Page seeded by [http://oca.weizmann.ac.il/oca OCA ] on Thu Feb 21 18:53:20 2008'' |
Revision as of 16:53, 21 February 2008
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COMPLEX STRUCTURE OF HUMAN IGF2R DOMAINS 11-13 BOUND TO IGF-II
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.
About this Structure
2V5P is a Protein complex structure of sequences from Homo sapiens with as ligand. Known structural/functional Sites: , , , , , and . Full crystallographic information is available from 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:18046459
Page seeded by OCA on Thu Feb 21 18:53:20 2008
Categories: Homo sapiens | Protein complex | Boxel, G Van. | Brown, J. | Delaine, C. | Denley, A. | Forbes, B E. | Gilbert, R J. | Hassan, A B. | Jones, E Y. | Siebold, C. | Wallace, J C. | Zaccheo, O J. | NAG | Beta barrel | Cation independent mannose 6-phosphate | Fibronectin type ii | Glycoprotein | Insulin-like growth factor | Lysosome | Membrane | Phosphorylation | Polymorphism | Receptor | Receptor/glycoprotein complex | Transmembrane | Transport
