2l29: Difference between revisions

Latest revision as of 08:16, 30 October 2024

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

Structural highlights

2l29 is a 2 chain structure with sequence from Homo sapiens. Full experimental information is available from OCA. For a guided tour on the structure components use FirstGlance.
Method:	Solution NMR, 20 models
Resources:	FirstGlance, OCA, PDBe, RCSB, PDBsum, ProSAT

Function

MPRI_HUMAN Transport of phosphorylated lysosomal enzymes from the Golgi complex and the cell surface to lysosomes. Lysosomal enzymes bearing phosphomannosyl residues bind specifically to mannose-6-phosphate receptors in the Golgi apparatus and the resulting receptor-ligand complex is transported to an acidic prelyosomal compartment where the low pH mediates the dissociation of the complex. This receptor also binds IGF2. Acts as a positive regulator of T-cell coactivation, by binding DPP4.^[1]

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^[2]

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

References

↑ Ikushima H, Munakata Y, Ishii T, Iwata S, Terashima M, Tanaka H, Schlossman SF, Morimoto C. Internalization of CD26 by mannose 6-phosphate/insulin-like growth factor II receptor contributes to T cell activation. Proc Natl Acad Sci U S A. 2000 Jul 18;97(15):8439-44. PMID:10900005
↑ 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:https://dx.doi.org/10.1126/science.1228633

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OCA

[1] Ikushima H, Munakata Y, Ishii T, Iwata S, Terashima M, Tanaka H, Schlossman SF, Morimoto C. Internalization of CD26 by mannose 6-phosphate/insulin-like growth factor II receptor contributes to T cell activation. Proc Natl Acad Sci U S A. 2000 Jul 18;97(15):8439-44. PMID:10900005

[2] 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:https://dx.doi.org/10.1126/science.1228633

[1]

[2]

@@ 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]]' scene=''>
 == Structural highlights ==
-<table><tr><td colspan='2'>[[2l29]] is a 2 chain structure with sequence from [https://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 [https://proteopedia.org/fgij/fg.htm?mol=2L29 FirstGlance]. <br>
+<table><tr><td colspan='2'>[[2l29]] 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=2L29 OCA]. For a <b>guided tour on the structure components</b> use [https://proteopedia.org/fgij/fg.htm?mol=2L29 FirstGlance]. <br>
-</td></tr><tr id='related'><td class="sblockLbl"><b>[[Related_structure|Related:]]</b></td><td class="sblockDat"><div style='overflow: auto; max-height: 3em;'>[[2cnj|2cnj]], [[1gp0|1gp0]], [[2l21|2l21]], [[2l2a|2l2a]]</div></td></tr>
+</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='gene'><td class="sblockLbl"><b>[[Gene|Gene:]]</b></td><td class="sblockDat">IGF2, PP1446 ([https://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'>[https://proteopedia.org/fgij/fg.htm?mol=2l29 FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=2l29 OCA], [https://pdbe.org/2l29 PDBe], [https://www.rcsb.org/pdb/explore.do?structureId=2l29 RCSB], [https://www.ebi.ac.uk/pdbsum/2l29 PDBsum], [https://prosat.h-its.org/prosat/prosatexe?pdbcode=2l29 ProSAT]</span></td></tr>
 </table>
-== 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 ==
-[[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>
+[https://www.uniprot.org/uniprot/MPRI_HUMAN MPRI_HUMAN] Transport of phosphorylated lysosomal enzymes from the Golgi complex and the cell surface to lysosomes. Lysosomal enzymes bearing phosphomannosyl residues bind specifically to mannose-6-phosphate receptors in the Golgi apparatus and the resulting receptor-ligand complex is transported to an acidic prelyosomal compartment where the low pH mediates the dissociation of the complex. This receptor also binds IGF2. Acts as a positive regulator of T-cell coactivation, by binding DPP4.<ref>PMID:10900005</ref>
 <div style="background-color:#fffaf0;">
 == Publication Abstract from PubMed ==
@@ Line 28: / Line 25: @@
 __TOC__
 </StructureSection>
-[[Category: Human]]
+[[Category: Homo sapiens]]
 [[Category: Large Structures]]
-[[Category: Crump, M P]]
+[[Category: Crump MP]]
-[[Category: Ellis, R Z]]
+[[Category: Ellis RZ]]
-[[Category: Forbes, B]]
+[[Category: Forbes B]]
-[[Category: Frago, S]]
+[[Category: Frago S]]
-[[Category: Hassan, A B]]
+[[Category: Hassan AB]]
-[[Category: Hoppe, H]]
+[[Category: Hoppe H]]
-[[Category: Jones, E Y]]
+[[Category: Jones EY]]
-[[Category: Prince, S N]]
+[[Category: Prince SN]]
-[[Category: Rezgui, D]]
+[[Category: Rezgui D]]
-[[Category: Strickland, M]]
+[[Category: Strickland M]]
-[[Category: Wattana-Amorn, P]]
+[[Category: Wattana-Amorn P]]
-[[Category: Williams, C]]
+[[Category: Williams C]]
-[[Category: Zaccheo, O J]]
+[[Category: Zaccheo OJ]]
-[[Category: Genomic imprinting]]
-[[Category: Insulin-like growth factor 2]]
-[[Category: Ligand trap]]
-[[Category: Mannose 6 phosphate receptor]]
-[[Category: Transport protein]]

2l29: Difference between revisions

Latest revision as of 08:16, 30 October 2024

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

Structural highlights

Function

Publication Abstract from PubMed

See Also

References

Contents

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