2V5O

STRUCTURE OF HUMAN IGF2R DOMAINS 11-14

2V5O の概要

• エントリーDOI: 10.2210/pdb2v5o/pdb
• 関連するPDBエントリー: 1E6F 1GP0 1GP3 1GQB 1JPL 1JWG 1LF8 2CNJ 2V5N 2V5P
• 分子名称: CATION-INDEPENDENT MANNOSE-6-PHOSPHATE RECEPTOR, 2-acetamido-2-deoxy-beta-D-glucopyranose, CHLORIDE ION (3 entities in total)
• 機能のキーワード: cation independent mannose 6-phosphate, membrane, receptor, lysosome, transport, beta barrel, phosphorylation, fibronectin type ii, insulin-like growth factor, glycoprotein, transmembrane
• 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: 70068.94

構造登録者

Brown, J.,Delaine, C.,Zaccheo, O.J.,Siebold, C.,Gilbert, R.J.,van Boxel, G.,Denley, A.,Wallace, J.C.,Hassan, A.B.,Forbes, B.E.,Jones, E.Y. (登録日: 2007-07-06, 公開日: 2007-12-11, 最終更新日: 2024-10-23)

主引用文献

Brown, J.,Delaine, C.,Zaccheo, O.J.,Siebold, C.,Gilbert, R.J.,Van Boxel, G.,Denley, A.,Wallace, J.C.,Hassan, A.B.,Forbes, B.E.,Jones, E.Y.
Structure and Functional Analysis of the Igf-II/Igf2R Interaction
Embo J., 27:265-, 2008

PubMed Abstract: Embryonic development and normal growth require exquisite control of insulin-like growth factors (IGFs). In mammals the extracellular region of the cation-independent mannose-6-phosphate receptor has gained an IGF-II-binding function and is termed type II IGF receptor (IGF2R). IGF2R sequesters IGF-II; imbalances occur in cancers and IGF2R is implicated in tumour suppression. We report crystal structures of IGF2R domains 11-12, 11-12-13-14 and domains 11-12-13/IGF-II complex. A distinctive juxtaposition of these domains provides the IGF-II-binding unit, with domain 11 directly interacting with IGF-II and domain 13 modulating binding site flexibility. Our complex shows that Phe19 and Leu53 of IGF-II lock into a hydrophobic pocket unique to domain 11 of mammalian IGF2Rs. Mutagenesis analyses confirm this IGF-II 'binding-hotspot', revealing that IGF-binding proteins and IGF2R have converged on the same high-affinity site.

PubMed: 18046459
DOI: 10.1038/SJ.EMBOJ.7601938

実験手法

X-RAY DIFFRACTION (2.91 Å)