2v5o | pdb_00002v5o

File:2v5o.jpg

spinqualitylabelsall models 2v5o, resolution 2.91Å Show:Asymmetric Unit Biological Assembly Drag the structure with the mouse to rotate   Export Animated Image   Print3D

STRUCTURE OF HUMAN IGF2R DOMAINS 11-14

Overview

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.

About this Structure

2V5O is a Single protein structure of sequence from Homo sapiens with NAG and CL as ligands. Known structural/functional Sites: AC1, AC2, AC3, AC4 and AC5. Full crystallographic information is available from OCA.

Reference

Structure and functional analysis of the IGF-II/IGF2R interaction., Brown J, Delaine C, Zaccheo OJ, Siebold C, Gilbert RJ, van Boxel G, Denley A, Wallace JC, Hassan AB, Forbes BE, Jones EY, EMBO J. 2008 Jan 9;27(1):265-76. Epub 2007 Nov 29. PMID:18046459

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