2v5p: Difference between revisions
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New page: left|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
|
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 NAG as ligand. Known structural/functional Sites: AC1, AC2, AC3, AC5, AC6, AC7 and AC8. 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
Proteopedia Page Contributors and Editors (what is this?)
Categories:
- Pages with broken file links
- 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
