2L29

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

Summary for 2L29

• Entry DOI: 10.2210/pdb2l29/pdb
• Related: 1GP0 2CNJ 2L21 2L2A
• NMR Information: BMRB: 17127
• Descriptor: Insulin-like growth factor 2 receptor variant, Insulin-like growth factor II (2 entities in total)
• Functional Keywords: mannose 6 phosphate receptor, insulin-like growth factor 2, genomic imprinting, ligand trap, transport protein
• Biological source: Homo sapiens (human); More
• Total number of polymer chains: 2
• Total formula weight: 22919.00

Authors

Williams, C.,Hoppe, H.,Rezgui, D.,Strickland, M.,Frago, S.,Ellis, R.Z.,Wattana-Amorn, P.,Prince, S.N.,Zaccheo, O.J.,Forbes, B.,Jones, E.Y.,Crump, M.P.,Hassan, A.B. (deposition date: 2010-08-13, release date: 2012-02-15, Last modification date: 2024-10-30)

Primary citation

Williams, 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

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

Experimental method

SOLUTION NMR