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Structure and functional analysis of the IGF-II/IGF2R interaction.
- Source :
- EMBO Journal; 1/9/2008, Vol. 27 Issue 1, p265-276, 12p, 7 Diagrams, 2 Charts
- Publication Year :
- 2008
-
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. [ABSTRACT FROM AUTHOR]
- Subjects :
- TUMORS
HYPOGLYCEMIC agents
GROWTH factors
CYTOKINES
GENETIC mutation
TERATOGENESIS
Subjects
Details
- Language :
- English
- ISSN :
- 02614189
- Volume :
- 27
- Issue :
- 1
- Database :
- Complementary Index
- Journal :
- EMBO Journal
- Publication Type :
- Academic Journal
- Accession number :
- 28154633
- Full Text :
- https://doi.org/10.1038/sj.emboj.7601938