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Insulin and IGF-I Receptor Structure and Binding Mechanism.
- Source :
- Mechanisms of Insulin Action; 2007, p1-32, 32p
- Publication Year :
- 2007
-
Abstract
- The insulin and IGF-I receptors are members of the superfamily of receptor tyrosine kinases (RTKs). Unlike most RTKs that are single-chain monomeric transmembrane polypeptides, the insulin and IGF-I receptors are covalent dimers composed of two extracellular α subunits and two transmembrane β subunits containing the tyrosine kinase domains. The α subunits contain the ligand binding sites, of which at least three subdomains have been defined by photoaffinity crosslinking, alanine-scanning mutagenesis or minimized receptor constructs. All RTKs are dimeric or oligomeric in the ligand-activated form. The residues of insulin involved in receptor binding have been mapped by alanine-scanning mutagenesis. They form at least two major epitopes that partially overlap with the dimer- and hexamer-forming surfaces of the insulin molecule, and we propose that insulin is using those surfaces to asymmetrically cross-link the two receptor α subunits. This mechanism provides a structural basis for high affinity binding and negative cooperativity, and probably also operates in the IGF-receptor interaction. It also provides a structural basis for the approximation and transphosphorylation of the kinase domains and triggering of the signalling cascade. [ABSTRACT FROM AUTHOR]
Details
- Language :
- English
- ISBNs :
- 9780387722030
- Database :
- Supplemental Index
- Journal :
- Mechanisms of Insulin Action
- Publication Type :
- Book
- Accession number :
- 33086930
- Full Text :
- https://doi.org/10.1007/978-0-387-72204-7_1