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2v5p

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2v5p, resolution 4.10Å ()
Sites: , , , , , and
Ligands:
Non-Standard Residues:
Domains: FN2, CIMR, IlGF
Related: 1gf2, 1igl, 1e6f, 1gp0, 1gp3, 1gqb, 1jpl, 1jwg, 1lf8, 2cnj, 2v5n, 2v5o
Resources: FirstGlance, OCA, PDBsum, RCSB
Coordinates: save as pdb, mmCIF, xml



COMPLEX STRUCTURE OF HUMAN IGF2R DOMAINS 11-13 BOUND TO IGF-II

Publication Abstract from PubMed

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.

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

From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine.

About this Structure

2V5P is a 4 chains structure of sequences from Homo sapiens. Full crystallographic information is available from OCA.

Reference

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

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