Crystal structure of the first three domains of the type-1 insulin-like growth factor receptor
- PMID: 9690478
- DOI: 10.1038/28668
Crystal structure of the first three domains of the type-1 insulin-like growth factor receptor
Abstract
The type-1 insulin-like growth-factor receptor (IGF-1R) and insulin receptor (IR) are closely related members of the tyrosine-kinase receptor superfamily. IR is essential for glucose homeostasis, whereas IGF-1R is involved in both normal growth and development and malignant transformation. Homologues of these receptors are found in animals as simple as cnidarians. The epidermal growth-factor receptor (EGFR) family is closely related to the IR family and has significant sequence identity to the extracellular portion we describe here. We now present the structure of the first three domains of IGF-IR (L1-Cys-rich-L2) determined to 2.6 A resolution. The L domains each consist of a single-stranded right-handed beta-helix. The Cys-rich region is composed of eight disulphide-bonded modules, seven of which form a rod-shaped domain with modules associated in an unusual manner. The three domains surround a central space of sufficient size to accommodate a ligand molecule. Although the fragment (residues 1-462) does not bind ligand, many of the determinants responsible for hormone binding and ligand specificity map to this central site. This structure therefore shows how the IR subfamily might interact with their ligands.
Similar articles
-
Solution structure of ectodomains of the insulin receptor family: the ectodomain of the type 1 insulin-like growth factor receptor displays asymmetry of ligand binding accompanied by limited conformational change.J Mol Biol. 2009 Dec 18;394(5):878-92. doi: 10.1016/j.jmb.2009.10.011. Epub 2009 Oct 14. J Mol Biol. 2009. PMID: 19835884
-
Insulin receptor structure and its implications for the IGF-1 receptor.Curr Opin Struct Biol. 2007 Dec;17(6):699-705. doi: 10.1016/j.sbi.2007.07.007. Epub 2007 Sep 11. Curr Opin Struct Biol. 2007. PMID: 17851071 Review.
-
Characterization of a comparative model of the extracellular domain of the epidermal growth factor receptor.Protein Sci. 2000 Feb;9(2):310-24. doi: 10.1110/ps.9.2.310. Protein Sci. 2000. PMID: 10716183 Free PMC article.
-
Structure of the insulin receptor ectodomain reveals a folded-over conformation.Nature. 2006 Sep 14;443(7108):218-21. doi: 10.1038/nature05106. Epub 2006 Sep 6. Nature. 2006. PMID: 16957736
-
Structural insights into ligand-induced activation of the insulin receptor.Acta Physiol (Oxf). 2008 Jan;192(1):3-9. doi: 10.1111/j.1748-1716.2007.01781.x. Acta Physiol (Oxf). 2008. PMID: 18171424 Review.
Cited by
-
Assembly of high-affinity insulin receptor agonists and antagonists from peptide building blocks.Proc Natl Acad Sci U S A. 2003 Apr 15;100(8):4435-9. doi: 10.1073/pnas.0830026100. Epub 2003 Apr 8. Proc Natl Acad Sci U S A. 2003. PMID: 12684539 Free PMC article.
-
The first three domains of the insulin receptor differ structurally from the insulin-like growth factor 1 receptor in the regions governing ligand specificity.Proc Natl Acad Sci U S A. 2006 Aug 15;103(33):12429-34. doi: 10.1073/pnas.0605395103. Epub 2006 Aug 7. Proc Natl Acad Sci U S A. 2006. PMID: 16894147 Free PMC article.
-
Functionally significant insulin-like growth factor I receptor mutations in centenarians.Proc Natl Acad Sci U S A. 2008 Mar 4;105(9):3438-42. doi: 10.1073/pnas.0705467105. Epub 2008 Mar 3. Proc Natl Acad Sci U S A. 2008. PMID: 18316725 Free PMC article.
-
Neuropeptidergic Signaling in the American Lobster Homarus americanus: New Insights from High-Throughput Nucleotide Sequencing.PLoS One. 2015 Dec 30;10(12):e0145964. doi: 10.1371/journal.pone.0145964. eCollection 2015. PLoS One. 2015. PMID: 26716450 Free PMC article.
-
All-Atom Structural Models of the Transmembrane Domains of Insulin and Type 1 Insulin-Like Growth Factor Receptors.Front Endocrinol (Lausanne). 2016 Jun 20;7:68. doi: 10.3389/fendo.2016.00068. eCollection 2016. Front Endocrinol (Lausanne). 2016. PMID: 27379020 Free PMC article.
Publication types
MeSH terms
Substances
Associated data
- Actions
LinkOut - more resources
Full Text Sources
Other Literature Sources
Molecular Biology Databases
Research Materials
Miscellaneous
