2v5p

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2v5p, resolution 4.10Å

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

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

2V5P is a Protein complex structure of sequences from Homo sapiens with as ligand. Known structural/functional Sites: , , , , , and . 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. 2007 Nov 29;. PMID:18046459

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