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5l3n

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Revision as of 13:05, 10 May 2019

D11 bound [N29, S39_PQ]-IGF-II

Structural highlights

5l3n is a 1 chain structure with sequence from Human. Full experimental information is available from OCA. For a guided tour on the structure components use FirstGlance.
Gene:	IGF2, PP1446 (HUMAN)
Resources:	FirstGlance, OCA, PDBe, RCSB, PDBsum, ProSAT

Disease

[IGF2_HUMAN] Epigenetic changes of DNA hypomethylation in IGF2 are a cause of Silver-Russell syndrome (SRS) [MIM: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.^[1]

Function

[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.^[2] 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.^[3]

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.

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^[4]

From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine.

References

↑ Bartholdi D, Krajewska-Walasek M, Ounap K, Gaspar H, Chrzanowska KH, Ilyana H, Kayserili H, Lurie IW, Schinzel A, Baumer A. Epigenetic mutations of the imprinted IGF2-H19 domain in Silver-Russell syndrome (SRS): results from a large cohort of patients with SRS and SRS-like phenotypes. J Med Genet. 2009 Mar;46(3):192-7. doi: 10.1136/jmg.2008.061820. Epub 2008 Dec 9. PMID:19066168 doi:10.1136/jmg.2008.061820
↑ Cornish J, Callon KE, Bava U, Watson M, Xu X, Lin JM, Chan VA, Grey AB, Naot D, Buchanan CM, Cooper GJ, Reid IR. Preptin, another peptide product of the pancreatic beta-cell, is osteogenic in vitro and in vivo. Am J Physiol Endocrinol Metab. 2007 Jan;292(1):E117-22. Epub 2006 Aug 15. PMID:16912056 doi:10.1152/ajpendo.00642.2005
↑ Cornish J, Callon KE, Bava U, Watson M, Xu X, Lin JM, Chan VA, Grey AB, Naot D, Buchanan CM, Cooper GJ, Reid IR. Preptin, another peptide product of the pancreatic beta-cell, is osteogenic in vitro and in vivo. Am J Physiol Endocrinol Metab. 2007 Jan;292(1):E117-22. Epub 2006 Aug 15. PMID:16912056 doi:10.1152/ajpendo.00642.2005
↑ 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. Probing Receptor Specificity by Sampling the Conformational Space of the Insulin-like Growth Factor II C-domain. J Biol Chem. 2016 Aug 10. pii: jbc.M116.741041. PMID:27510031 doi:http://dx.doi.org/10.1074/jbc.M116.741041

1 Structural highlights
2 Disease
3 Function
4 Publication Abstract from PubMed
5 See Also
6 References

Proteopedia Page Contributors and Editors (what is this?)

OCA

Retrieved from "http://52.214.119.220/wiki/index.php/5l3n"

Categories: Human | Large Structures | Hexnerova, R | Cell cycle | Igf-ii

@@ Line 1: / Line 1: @@
 ==D11 bound [N29, S39_PQ]-IGF-II==
-<StructureSection load='5l3n' size='340' side='right' caption='[[5l3n]], [[NMR_Ensembles_of_Models | 20 NMR models]]' scene=''>
+<StructureSection load='5l3n' size='340' side='right'caption='[[5l3n]], [[NMR_Ensembles_of_Models | 20 NMR models]]' scene=''>
 == Structural highlights ==
-<table><tr><td colspan='2'>[[5l3n]] is a 1 chain structure. Full experimental information is available from [http://oca.weizmann.ac.il/oca-bin/ocashort?id=5L3N OCA]. For a <b>guided tour on the structure components</b> use [http://oca.weizmann.ac.il/oca-docs/fgij/fg.htm?mol=5L3N FirstGlance]. <br>
+<table><tr><td colspan='2'>[[5l3n]] is a 1 chain structure with sequence from [http://en.wikipedia.org/wiki/Human Human]. Full experimental information is available from [http://oca.weizmann.ac.il/oca-bin/ocashort?id=5L3N OCA]. For a <b>guided tour on the structure components</b> use [http://oca.weizmann.ac.il/oca-docs/fgij/fg.htm?mol=5L3N FirstGlance]. <br>
-</td></tr><tr id='resources'><td class="sblockLbl"><b>Resources:</b></td><td class="sblockDat"><span class='plainlinks'>[http://oca.weizmann.ac.il/oca-docs/fgij/fg.htm?mol=5l3n FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=5l3n OCA], [http://pdbe.org/5l3n PDBe], [http://www.rcsb.org/pdb/explore.do?structureId=5l3n RCSB], [http://www.ebi.ac.uk/pdbsum/5l3n PDBsum], [http://prosat.h-its.org/prosat/prosatexe?pdbcode=5l3n ProSAT]</span></td></tr>
+</td></tr><tr id='gene'><td class="sblockLbl"><b>[[Gene|Gene:]]</b></td><td class="sblockDat">IGF2, PP1446 ([http://www.ncbi.nlm.nih.gov/Taxonomy/Browser/wwwtax.cgi?mode=Info&srchmode=5&id=9606 HUMAN])</td></tr>
+<tr id='resources'><td class="sblockLbl"><b>Resources:</b></td><td class="sblockDat"><span class='plainlinks'>[http://oca.weizmann.ac.il/oca-docs/fgij/fg.htm?mol=5l3n FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=5l3n OCA], [http://pdbe.org/5l3n PDBe], [http://www.rcsb.org/pdb/explore.do?structureId=5l3n RCSB], [http://www.ebi.ac.uk/pdbsum/5l3n PDBsum], [http://prosat.h-its.org/prosat/prosatexe?pdbcode=5l3n ProSAT]</span></td></tr>
 </table>
 == Disease ==
@@ Line 19: / Line 20: @@
 </div>
 <div class="pdbe-citations 5l3n" style="background-color:#fffaf0;"></div>
+==See Also==
+*[[Insulin-like growth factor|Insulin-like growth factor]]
 == References ==
 <references/>
 __TOC__
 </StructureSection>
+[[Category: Human]]
+[[Category: Large Structures]]
 [[Category: Hexnerova, R]]
 [[Category: Cell cycle]]
 [[Category: Igf-ii]]

5l3n

From Proteopedia

Revision as of 13:05, 10 May 2019

D11 bound [N29, S39_PQ]-IGF-II

Structural highlights

Disease

Function

Publication Abstract from PubMed

See Also

References

Contents

Proteopedia Page Contributors and Editors (what is this?)

Views

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