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2l29

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Revision as of 08:31, 5 February 2020

Complex structure of E4 mutant human IGF2R domain 11 bound to IGF-II

Structural highlights

2l29 is a 2 chain structure with sequence from Human. Full experimental information is available from OCA. For a guided tour on the structure components use FirstGlance.
Related:	2cnj, 1gp0, 2l21, 2l2a
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

Placental development and genomic imprinting coevolved with parental conflict over resource distribution to mammalian offspring. The imprinted genes IGF2 and IGF2R code for the growth promoter insulin-like growth factor 2 (IGF2) and its inhibitor, mannose 6-phosphate (M6P)/IGF2 receptor (IGF2R), respectively. M6P/IGF2R of birds and fish do not recognize IGF2. In monotremes, which lack imprinting, IGF2 specifically bound M6P/IGF2R via a hydrophobic CD loop. We show that the DNA coding the CD loop in monotremes functions as an exon splice enhancer (ESE) and that structural evolution of binding site loops (AB, HI, FG) improved therian IGF2 affinity. We propose that ESE evolution led to the fortuitous acquisition of IGF2 binding by M6P/IGF2R that drew IGF2R into parental conflict; subsequent imprinting may then have accelerated affinity maturation.

An exon splice enhancer primes IGF2:IGF2R binding site structure and function evolution.,Williams C, Hoppe HJ, Rezgui D, Strickland M, Forbes BE, Grutzner F, Frago S, Ellis RZ, Wattana-Amorn P, Prince SN, Zaccheo OJ, Nolan CM, Mungall AJ, Jones EY, Crump MP, Hassan AB Science. 2012 Nov 30;338(6111):1209-13. doi: 10.1126/science.1228633. PMID:23197533^[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
↑ Williams C, Hoppe HJ, Rezgui D, Strickland M, Forbes BE, Grutzner F, Frago S, Ellis RZ, Wattana-Amorn P, Prince SN, Zaccheo OJ, Nolan CM, Mungall AJ, Jones EY, Crump MP, Hassan AB. An exon splice enhancer primes IGF2:IGF2R binding site structure and function evolution. Science. 2012 Nov 30;338(6111):1209-13. doi: 10.1126/science.1228633. PMID:23197533 doi:http://dx.doi.org/10.1126/science.1228633

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/2l29"

@@ Line 1: / Line 1: @@
 ==Complex structure of E4 mutant human IGF2R domain 11 bound to IGF-II==
-<StructureSection load='2l29' size='340' side='right' caption='[[2l29]], [[NMR_Ensembles_of_Models | 20 NMR models]]' scene=''>
+<StructureSection load='2l29' size='340' side='right'caption='[[2l29]], [[NMR_Ensembles_of_Models | 20 NMR models]]' scene=''>
 == Structural highlights ==
 <table><tr><td colspan='2'>[[2l29]] is a 2 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=2L29 OCA]. For a <b>guided tour on the structure components</b> use [http://oca.weizmann.ac.il/oca-docs/fgij/fg.htm?mol=2L29 FirstGlance]. <br>
@@ Line 29: / Line 29: @@
 </StructureSection>
 [[Category: Human]]
+[[Category: Large Structures]]
 [[Category: Crump, M P]]
 [[Category: Ellis, R Z]]

2l29

From Proteopedia

Revision as of 08:31, 5 February 2020

Complex structure of E4 mutant human IGF2R domain 11 bound to IGF-II

Structural highlights

Disease

Function

Publication Abstract from PubMed

See Also

References

Contents

Proteopedia Page Contributors and Editors (what is this?)

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