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==STRUCTURE OF THE IGF BINDING DOMAIN OF THE INSULIN-LIKE GROWTH FACTOR-BINDING PROTEIN-5 (IGFBP-5): IMPLICATIONS FOR IGF AND IGF-I RECEPTOR INTERACTIONS==
==STRUCTURE OF THE IGF BINDING DOMAIN OF THE INSULIN-LIKE GROWTH FACTOR-BINDING PROTEIN-5 (IGFBP-5): IMPLICATIONS FOR IGF AND IGF-I RECEPTOR INTERACTIONS==
<StructureSection load='1boe' size='340' side='right'caption='[[1boe]], [[NMR_Ensembles_of_Models | 20 NMR models]]' scene=''>
<StructureSection load='1boe' size='340' side='right'caption='[[1boe]]' scene=''>
== Structural highlights ==
== Structural highlights ==
<table><tr><td colspan='2'>[[1boe]] is a 1 chain structure with sequence from [https://en.wikipedia.org/wiki/Homo_sapiens Homo sapiens]. Full experimental information is available from [http://oca.weizmann.ac.il/oca-bin/ocashort?id=1BOE OCA]. For a <b>guided tour on the structure components</b> use [https://proteopedia.org/fgij/fg.htm?mol=1BOE FirstGlance]. <br>
<table><tr><td colspan='2'>[[1boe]] is a 1 chain structure with sequence from [https://en.wikipedia.org/wiki/Homo_sapiens Homo sapiens]. Full experimental information is available from [http://oca.weizmann.ac.il/oca-bin/ocashort?id=1BOE OCA]. For a <b>guided tour on the structure components</b> use [https://proteopedia.org/fgij/fg.htm?mol=1BOE FirstGlance]. <br>
</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=1boe FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=1boe OCA], [https://pdbe.org/1boe PDBe], [https://www.rcsb.org/pdb/explore.do?structureId=1boe RCSB], [https://www.ebi.ac.uk/pdbsum/1boe PDBsum], [https://prosat.h-its.org/prosat/prosatexe?pdbcode=1boe ProSAT]</span></td></tr>
</td></tr><tr id='method'><td class="sblockLbl"><b>[[Empirical_models|Method:]]</b></td><td class="sblockDat" id="methodDat">Solution NMR</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=1boe FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=1boe OCA], [https://pdbe.org/1boe PDBe], [https://www.rcsb.org/pdb/explore.do?structureId=1boe RCSB], [https://www.ebi.ac.uk/pdbsum/1boe PDBsum], [https://prosat.h-its.org/prosat/prosatexe?pdbcode=1boe ProSAT]</span></td></tr>
</table>
</table>
== Function ==
== Function ==
[[https://www.uniprot.org/uniprot/IBP5_HUMAN IBP5_HUMAN]] IGF-binding proteins prolong the half-life of the IGFs and have been shown to either inhibit or stimulate the growth promoting effects of the IGFs on cell culture. They alter the interaction of IGFs with their cell surface receptors.  
[https://www.uniprot.org/uniprot/IBP5_HUMAN IBP5_HUMAN] IGF-binding proteins prolong the half-life of the IGFs and have been shown to either inhibit or stimulate the growth promoting effects of the IGFs on cell culture. They alter the interaction of IGFs with their cell surface receptors.
== Evolutionary Conservation ==
== Evolutionary Conservation ==
[[Image:Consurf_key_small.gif|200px|right]]
[[Image:Consurf_key_small.gif|200px|right]]
Line 18: Line 19:
</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=1boe ConSurf].
</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=1boe ConSurf].
<div style="clear:both"></div>
<div style="clear:both"></div>
<div style="background-color:#fffaf0;">
== Publication Abstract from PubMed ==
Binding proteins for insulin-like growth factors (IGFs) IGF-I and IGF-II, known as IGFBPs, control the distribution, function and activity of IGFs in various cell tissues and body fluids. Insulin-like growth factor-binding protein-5 (IGFBP-5) is known to modulate the stimulatory effects of IGFs and is the major IGF-binding protein in bone tissue. We have expressed two N-terminal fragments of IGFBP-5 in Escherichia coli; the first encodes the N-terminal domain of the protein (residues 1-104) and the second, mini-IGFBP-5, comprises residues Ala40 to Ile92. We show that the entire IGFBP-5 protein contains only one high-affinity binding site for IGFs, located in mini-IGFBP-5. The solution structure of mini-IGFBP-5, determined by nuclear magnetic resonance spectroscopy, discloses a rigid, globular structure that consists of a centrally located three-stranded anti-parallel beta-sheet. Its scaffold is stabilized further by two inside packed disulfide bridges. The binding to IGFs, which is in the nanomolar range, involves conserved Leu and Val residues localized in a hydrophobic patch on the surface of the IGFBP-5 protein. Remarkably, the IGF-I receptor binding assays of IGFBP-5 showed that IGFBP-5 inhibits the binding of IGFs to the IGF-I receptor, resulting in reduction of receptor stimulation and autophosphorylation. Compared with the full-length IGFBP-5, the smaller N-terminal fragments were less efficient inhibitors of the IGF-I receptor binding of IGFs.
Structure of the IGF-binding domain of the insulin-like growth factor-binding protein-5 (IGFBP-5): implications for IGF and IGF-I receptor interactions.,Kalus W, Zweckstetter M, Renner C, Sanchez Y, Georgescu J, Grol M, Demuth D, Schumacher R, Dony C, Lang K, Holak TA EMBO J. 1998 Nov 16;17(22):6558-72. PMID:9822601<ref>PMID:9822601</ref>
From MEDLINE&reg;/PubMed&reg;, a database of the U.S. National Library of Medicine.<br>
</div>
<div class="pdbe-citations 1boe" style="background-color:#fffaf0;"></div>


==See Also==
==See Also==
*[[Insulin-like growth factor binding protein 3D structures|Insulin-like growth factor binding protein 3D structures]]
*[[Insulin-like growth factor binding protein 3D structures|Insulin-like growth factor binding protein 3D structures]]
== References ==
<references/>
__TOC__
__TOC__
</StructureSection>
</StructureSection>
[[Category: Homo sapiens]]
[[Category: Homo sapiens]]
[[Category: Large Structures]]
[[Category: Large Structures]]
[[Category: Demuth, D]]
[[Category: Demuth D]]
[[Category: Georgescu, J]]
[[Category: Georgescu J]]
[[Category: Grol, M]]
[[Category: Grol M]]
[[Category: Holak, T H]]
[[Category: Holak TH]]
[[Category: Kalus, W]]
[[Category: Kalus W]]
[[Category: Lang, K]]
[[Category: Lang K]]
[[Category: Renner, C]]
[[Category: Renner C]]
[[Category: Sanchez, Y]]
[[Category: Sanchez Y]]
[[Category: Schumacherdony, C]]
[[Category: Schumacherdony C]]
[[Category: Zweckstetter, M]]
[[Category: Zweckstetter M]]
[[Category: Hormone-growth factor complex]]
[[Category: Igf]]
[[Category: Igfbp-5]]
[[Category: Insulin-like growth factor binding protein]]
[[Category: Mini-igfbp-5]]

Revision as of 15:34, 13 March 2024

STRUCTURE OF THE IGF BINDING DOMAIN OF THE INSULIN-LIKE GROWTH FACTOR-BINDING PROTEIN-5 (IGFBP-5): IMPLICATIONS FOR IGF AND IGF-I RECEPTOR INTERACTIONS

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