2L2A
Mutated Domain 11 of the Cytoplasmic region of the Cation-independent mannose-6-phosphate receptor
Summary for 2L2A
| Entry DOI | 10.2210/pdb2l2a/pdb |
| Related | 1GP0 2CNJ 2L21 2L29 |
| Descriptor | Insulin-like growth factor 2 receptor variant (1 entity in total) |
| Functional Keywords | mannose 6 phosphate receptor, protein evolution, insulin-like growth factor 2, genomic imprinting, transport protein |
| Biological source | Homo sapiens (human) |
| Total number of polymer chains | 1 |
| Total formula weight | 15434.52 |
| 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: 2012-12-12) |
| 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 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: 23197533DOI: 10.1126/science.1228633 PDB entries with the same primary citation |
| Experimental method | SOLUTION NMR |
Structure validation
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