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2LLA

NMR solution structure ensemble of domain 11 of the echidna M6P/IGF2R receptor

Summary for 2LLA
Entry DOI10.2210/pdb2lla/pdb
Related2CNJ
NMR InformationBMRB: 17287
DescriptorMannose-6-phosphate/insulin-like growth factor II receptor (1 entity in total)
Functional Keywordsmonotreme, mannose-6-phosphate, igf-ii, domain 11, transport protein
Biological sourceTachyglossus aculeatus (short-beaked echidna)
Total number of polymer chains1
Total formula weight15298.32
Authors
Strickland, M.,Crump, M.P.,Williams, C.,Rezgui, D.,Ellis, R.Z.,Hoppe, H.,Frago, S.,Prince, S.N.,Zaccheo, O.J.,Forbes, B.E.,Jones, E.,Hassan, A.Z.,Wattana-Amorn, P. (deposition date: 2011-11-05, release date: 2012-11-07, Last modification date: 2024-10-16)
Primary citationWilliams, C.,Hoppe, H.J.,Rezgui, D.,Strickland, M.,Forbes, B.E.,Grutzner, F.,Frago, S.,Ellis, R.Z.,Wattana-Amorn, P.,Prince, S.N.,Zaccheo, O.J.,Nolan, C.M.,Mungall, A.J.,Jones, E.Y.,Crump, M.P.,Hassan, A.B.
An exon splice enhancer primes IGF2:IGF2R binding site structure and function evolution.
Science, 338:1209-1213, 2012
Cited by
PubMed Abstract: 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.
PubMed: 23197533
DOI: 10.1126/science.1228633
PDB entries with the same primary citation
Experimental method
SOLUTION NMR
Structure validation

226707

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