Title : 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