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[[Image:1pmx.gif|left|200px]]
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{{STRUCTURE_1pmx|  PDB=1pmx  |  SCENE=  }}
'''INSULIN-LIKE GROWTH FACTOR-I BOUND TO A PHAGE-DERIVED PEPTIDE'''


==INSULIN-LIKE GROWTH FACTOR-I BOUND TO A PHAGE-DERIVED PEPTIDE==
<StructureSection load='1pmx' size='340' side='right'caption='[[1pmx]]' scene=''>
== Structural highlights ==
<table><tr><td colspan='2'>[[1pmx]] is a 2 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=1PMX OCA]. For a <b>guided tour on the structure components</b> use [https://proteopedia.org/fgij/fg.htm?mol=1PMX FirstGlance]. <br>
</td></tr><tr id='method'><td class="sblockLbl"><b>[[Empirical_models|Method:]]</b></td><td class="sblockDat" id="methodDat">Solution NMR, 20 models</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=1pmx FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=1pmx OCA], [https://pdbe.org/1pmx PDBe], [https://www.rcsb.org/pdb/explore.do?structureId=1pmx RCSB], [https://www.ebi.ac.uk/pdbsum/1pmx PDBsum], [https://prosat.h-its.org/prosat/prosatexe?pdbcode=1pmx ProSAT]</span></td></tr>
</table>
== Disease ==
[https://www.uniprot.org/uniprot/IGF1_HUMAN IGF1_HUMAN] Defects in IGF1 are the cause of insulin-like growth factor I deficiency (IGF1 deficiency) [MIM:[https://omim.org/entry/608747 608747]. IGF1 deficiency is an autosomal recessive disorder characterized by growth retardation, sensorineural deafness and mental retardation.
== Function ==
[https://www.uniprot.org/uniprot/IGF1_HUMAN IGF1_HUMAN] The insulin-like growth factors, isolated from plasma, are structurally and functionally related to insulin but have a much higher growth-promoting activity. May be a physiological regulator of [1-14C]-2-deoxy-D-glucose (2DG) transport and glycogen synthesis in osteoblasts. Stimulates glucose transport in rat bone-derived osteoblastic (PyMS) cells and is effective at much lower concentrations than insulin, not only regarding glycogen and DNA synthesis but also with regard to enhancing glucose uptake.<ref>PMID:21076856</ref>
== Evolutionary Conservation ==
[[Image:Consurf_key_small.gif|200px|right]]
Check<jmol>
  <jmolCheckbox>
    <scriptWhenChecked>; select protein; define ~consurf_to_do selected; consurf_initial_scene = true; script "/wiki/ConSurf/pm/1pmx_consurf.spt"</scriptWhenChecked>
    <scriptWhenUnchecked>script /wiki/extensions/Proteopedia/spt/initialview03.spt</scriptWhenUnchecked>
    <text>to colour the structure by Evolutionary Conservation</text>
  </jmolCheckbox>
</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=1pmx ConSurf].
<div style="clear:both"></div>
<div style="background-color:#fffaf0;">
== Publication Abstract from PubMed ==
The dramatic improvement in the NMR spectra of insulin-like growth factor I (IGF-I) in the presence of a peptide identified from a phage display library has allowed for the first time the determination of a high-resolution solution structure for much of IGF-I. The three helices of IGF-I in this complex have an arrangement similar to that seen in high-resolution crystal structures of IGF-I and insulin, although there are differences in the conformation and precise location of helix 3. A cluster of hydrophobic and basic side chains within the turn-helix motif of the peptide contact a hydrophobic patch on helices 1 and 3 of IGF-I. The importance of this patch for tight binding was verified using alanine scanning mutagenesis of the peptide in two different phage display formats. Consistent with its antagonistic activity, the peptide binds to a region implicated by mutagenesis studies to be important for association with IGF binding proteins (IGFBPs). The ability of the peptide to also inhibit signaling has important implications for the manner in which IGF-I interacts with its receptor. Interestingly, the peptide uses the same binding site as detergent and a fragment of IGFBP-5 identified in other IGF-I complexes. The ligand-induced structural variability of helix 3 in these complexes suggests that exchange between such conformations may be the source of the dynamic nature of free IGF-I and likely has functional significance for the ability of IGF-I to recognize two signaling receptors and six binding proteins with high affinity.


==Overview==
Complex with a phage display-derived peptide provides insight into the function of insulin-like growth factor I.,Schaffer ML, Deshayes K, Nakamura G, Sidhu S, Skelton NJ Biochemistry. 2003 Aug 12;42(31):9324-34. PMID:12899619<ref>PMID:12899619</ref>
The dramatic improvement in the NMR spectra of insulin-like growth factor I (IGF-I) in the presence of a peptide identified from a phage display library has allowed for the first time the determination of a high-resolution solution structure for much of IGF-I. The three helices of IGF-I in this complex have an arrangement similar to that seen in high-resolution crystal structures of IGF-I and insulin, although there are differences in the conformation and precise location of helix 3. A cluster of hydrophobic and basic side chains within the turn-helix motif of the peptide contact a hydrophobic patch on helices 1 and 3 of IGF-I. The importance of this patch for tight binding was verified using alanine scanning mutagenesis of the peptide in two different phage display formats. Consistent with its antagonistic activity, the peptide binds to a region implicated by mutagenesis studies to be important for association with IGF binding proteins (IGFBPs). The ability of the peptide to also inhibit signaling has important implications for the manner in which IGF-I interacts with its receptor. Interestingly, the peptide uses the same binding site as detergent and a fragment of IGFBP-5 identified in other IGF-I complexes. The ligand-induced structural variability of helix 3 in these complexes suggests that exchange between such conformations may be the source of the dynamic nature of free IGF-I and likely has functional significance for the ability of IGF-I to recognize two signaling receptors and six binding proteins with high affinity.


==About this Structure==
From MEDLINE&reg;/PubMed&reg;, a database of the U.S. National Library of Medicine.<br>
1PMX 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=1PMX OCA].
</div>
<div class="pdbe-citations 1pmx" style="background-color:#fffaf0;"></div>


==Reference==
==See Also==
Complex with a phage display-derived peptide provides insight into the function of insulin-like growth factor I., Schaffer ML, Deshayes K, Nakamura G, Sidhu S, Skelton NJ, Biochemistry. 2003 Aug 12;42(31):9324-34. PMID:[http://www.ncbi.nlm.nih.gov/pubmed/12899619 12899619]
*[[Insulin-like growth factor|Insulin-like growth factor]]
== References ==
<references/>
__TOC__
</StructureSection>
[[Category: Homo sapiens]]
[[Category: Homo sapiens]]
[[Category: Single protein]]
[[Category: Large Structures]]
[[Category: Skelton, N J.]]
[[Category: Skelton NJ]]
[[Category: High affinity ligand]]
[[Category: Igf-i]]
[[Category: Peptide binding]]
''Page seeded by [http://oca.weizmann.ac.il/oca OCA ] on Sat May  3 05:15:55 2008''
Retrieved from "https://proteopedia.org/1pmx"