5l3l
From Proteopedia
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==D11 bound IGF-II== | ==D11 bound IGF-II== | ||
| - | <StructureSection load='5l3l' size='340' side='right' caption='[[5l3l | + | <StructureSection load='5l3l' size='340' side='right'caption='[[5l3l]]' scene=''> |
== Structural highlights == | == Structural highlights == | ||
| - | <table><tr><td colspan='2'>[[5l3l]] is a 1 chain structure. Full experimental information is available from [http://oca.weizmann.ac.il/oca-bin/ocashort?id=5L3L OCA]. For a <b>guided tour on the structure components</b> use [ | + | <table><tr><td colspan='2'>[[5l3l]] 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=5L3L OCA]. For a <b>guided tour on the structure components</b> use [https://proteopedia.org/fgij/fg.htm?mol=5L3L FirstGlance]. <br> |
| - | </td></tr><tr id='resources'><td class="sblockLbl"><b>Resources:</b></td><td class="sblockDat"><span class='plainlinks'>[ | + | </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=5l3l FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=5l3l OCA], [https://pdbe.org/5l3l PDBe], [https://www.rcsb.org/pdb/explore.do?structureId=5l3l RCSB], [https://www.ebi.ac.uk/pdbsum/5l3l PDBsum], [https://prosat.h-its.org/prosat/prosatexe?pdbcode=5l3l ProSAT]</span></td></tr> | ||
</table> | </table> | ||
== Disease == | == Disease == | ||
| - | [ | + | [https://www.uniprot.org/uniprot/IGF2_HUMAN IGF2_HUMAN] Epigenetic changes of DNA hypomethylation in IGF2 are a cause of Silver-Russell syndrome (SRS) [MIM:[https://omim.org/entry/180860 180860]. A clinically heterogeneous condition characterized by severe intrauterine growth retardation, poor postnatal growth, craniofacial features such as a triangular shaped face and a broad forehead, body asymmetry, and a variety of minor malformations. The phenotypic expression changes during childhood and adolescence, with the facial features and asymmetry usually becoming more subtle with age.<ref>PMID:19066168</ref> |
== Function == | == Function == | ||
| - | [ | + | [https://www.uniprot.org/uniprot/IGF2_HUMAN IGF2_HUMAN] The insulin-like growth factors possess growth-promoting activity. In vitro, they are potent mitogens for cultured cells. IGF-II is influenced by placental lactogen and may play a role in fetal development.<ref>PMID:16912056</ref> Preptin undergoes glucose-mediated co-secretion with insulin, and acts as physiological amplifier of glucose-mediated insulin secretion. Exhibits osteogenic properties by increasing osteoblast mitogenic activity through phosphoactivation of MAPK1 and MAPK3.<ref>PMID:16912056</ref> |
| + | <div style="background-color:#fffaf0;"> | ||
| + | == Publication Abstract from PubMed == | ||
| + | Insulin and insulin-like growth factors I and II are closely related protein hormones. Their distinct evolution has resulted in different yet overlapping biological functions, with insulin becoming a key regulator of metabolism, while IGF-I/II are major growth factors. Insulin and IGFs cross-bind with different affinities to closely related insulin receptor isoforms A and B (IR-A and IR-B) and IGF-I receptor (IGF-1R). Identification of structural determinants in IGFs and insulin that trigger their specific signaling pathways is of increasing importance in designing receptor specific analogs with potential therapeutic applications. Here, we developed a straightforward protocol for production of recombinant IGF-II and prepared six IGF-II analogs with IGF-I-like mutations. All modified molecules exhibit significantly reduced affinity towards IR-A, particularly the analogs with Pro-Gln insertion in the C-domain. Moreover, one of the analogs has enhanced binding affinity for IGF-1R due to a synergistic effect of the Pro-Gln insertion and Ser29Asn point mutation. Consequently, this analog has almost a 10-fold higher IGF-1R/IR-A binding specificity in comparison with native IGF-II. The established IGF-II purification protocol allowed for a cost-effective isotope labeling required for a detailed NMR structural characterization of IGF-II analogs that revealed a link between the altered binding behavior of selected analogs and conformational rearrangement of their C-domain. | ||
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| + | Probing Receptor Specificity by Sampling the Conformational Space of the Insulin-like Growth Factor II C-domain.,Hexnerova R, Krizkova K, Fabry M, Sieglova I, Kedrova K, Collinsova M, Ullrichova P, Srb P, Williams C, Crump MP, Tosner Z, Jiracek J, Veverka V, Zakova L J Biol Chem. 2016 Aug 10. pii: jbc.M116.741041. PMID:27510031<ref>PMID:27510031</ref> | ||
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| + | From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine.<br> | ||
| + | </div> | ||
| + | <div class="pdbe-citations 5l3l" style="background-color:#fffaf0;"></div> | ||
| + | |||
| + | ==See Also== | ||
| + | *[[Insulin-like growth factor|Insulin-like growth factor]] | ||
| + | *[[Lysozyme 3D structures|Lysozyme 3D structures]] | ||
== References == | == References == | ||
<references/> | <references/> | ||
__TOC__ | __TOC__ | ||
</StructureSection> | </StructureSection> | ||
| - | [[Category: | + | [[Category: Homo sapiens]] |
| - | [[Category: | + | [[Category: Large Structures]] |
| - | [[Category: | + | [[Category: Hexnerova R]] |
Current revision
D11 bound IGF-II
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