2L2A

Mutated Domain 11 of the Cytoplasmic region of the Cation-independent mannose-6-phosphate receptor

2L2A の概要

• エントリーDOI: 10.2210/pdb2l2a/pdb
• 関連するPDBエントリー: 1GP0 2CNJ 2L21 2L29
• 分子名称: Insulin-like growth factor 2 receptor variant (1 entity in total)
• 機能のキーワード: mannose 6 phosphate receptor, protein evolution, insulin-like growth factor 2, genomic imprinting, transport protein
• 由来する生物種: Homo sapiens (human)
• タンパク質・核酸の鎖数: 1
• 化学式量合計: 15434.52

構造登録者

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. (登録日: 2010-08-13, 公開日: 2012-02-15, 最終更新日: 2024-11-20)

主引用文献

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

実験手法

SOLUTION NMR