View source for 2l29


==Complex structure of E4 mutant human IGF2R domain 11 bound to IGF-II==
<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/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='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=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>
== Function ==
[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 ==
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&reg;/PubMed&reg;, a database of the U.S. National Library of Medicine.<br>
</div>
<div class="pdbe-citations 2l29" 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]]