2l2a: Difference between revisions
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==Mutated Domain 11 of the Cytoplasmic region of the Cation-independent mannose-6-phosphate receptor== | |||
<StructureSection load='2l2a' size='340' side='right'caption='[[2l2a]]' scene=''> | |||
== Structural highlights == | |||
<table><tr><td colspan='2'>[[2l2a]] 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=2L2A OCA]. For a <b>guided tour on the structure components</b> use [https://proteopedia.org/fgij/fg.htm?mol=2L2A 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=2l2a FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=2l2a OCA], [https://pdbe.org/2l2a PDBe], [https://www.rcsb.org/pdb/explore.do?structureId=2l2a RCSB], [https://www.ebi.ac.uk/pdbsum/2l2a PDBsum], [https://prosat.h-its.org/prosat/prosatexe?pdbcode=2l2a ProSAT]</span></td></tr> | |||
</table> | |||
<div style="background-color:#fffaf0;"> | |||
== 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<ref>PMID:23197533</ref> | |||
From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine.<br> | |||
</div> | |||
<div class="pdbe-citations 2l2a" style="background-color:#fffaf0;"></div> | |||
==See Also== | |||
*[[Insulin-like growth factor receptor|Insulin-like growth factor receptor]] | |||
== References == | |||
<references/> | |||
__TOC__ | |||
</StructureSection> | |||
[[Category: Homo sapiens]] | |||
[[Category: Large Structures]] | |||
[[Category: Crump MP]] | |||
[[Category: Ellis RZ]] | |||
[[Category: Forbes B]] | |||
[[Category: Frago S]] | |||
[[Category: Hassan AB]] | |||
[[Category: Hoppe H]] | |||
[[Category: Jones EY]] | |||
[[Category: Prince SN]] | |||
[[Category: Rezgui D]] | |||
[[Category: Strickland M]] | |||
[[Category: Wattana-Amorn P]] | |||
[[Category: Williams C]] | |||
[[Category: Zaccheo OJ]] | |||
Latest revision as of 04:09, 21 November 2024
Mutated Domain 11 of the Cytoplasmic region of the Cation-independent mannose-6-phosphate receptorMutated Domain 11 of the Cytoplasmic region of the Cation-independent mannose-6-phosphate receptor
Structural highlights
Publication Abstract from PubMedPlacental 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[1] From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine. See AlsoReferences
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