Insulin receptor structure and its implications for the IGF-1 receptor.
The insulin receptor (isoforms IR-A and IR-B) and the type-I insulin-like growth factor receptor (IGF-1R) are homologous, multi-domain tyrosine kinases that bind insulin and IGF-1 with differing specificity. IR is involved in metabolic regulation and IGF-1R in normal growth and development. IR-A also binds IGF-2 with an affinity comparable to IGF-1R and, like the latter, is implicated in a range of cancers. The recent structure of the IR ectodomain dimer explains many features of ligand-receptor binding and provides insight into the structure of the intact ligand-binding site in both receptors. The structures of the L1-CR-L2 fragments of IR and IGF-1R reveal major differences in the regions that govern ligand specificity. The IR ectodomain X-ray structure raises doubts about that obtained by STEM reconstruction.
Lawrence
Michael C
MC
Walter and Eliza Hall Institute of Medical Research, 1G Royal Parade, Parkville, Victoria 3050, Australia.
McKern
Neil M
NM
Ward
Colin W
CW
D000818:Animals; D006801:Humans; D008024:Ligands; D008958:Models, Molecular; D011487:Protein Conformation; D017526:Receptor, IGF Type 1 / Q000737:chemistry* / Q000378:metabolism; D011972:Receptor, Insulin / Q000737:chemistry* / Q000378:metabolism
D008024:Ligands; D017526:Receptor, IGF Type 1; D011972:Receptor, Insulin