Chapter category: Endocrine

Insulin and IGF-I Receptor Structure and Binding Mechanism

This chapter appears in the following book:

Mechanisms of Insulin Action

Edited by: Alan R. Saltiel and Jeffrey E. Pessin
ISBN: 978-0-387-72203-0
» Get more information about this book at landesbioscience.com «

Chapter authors:
Pierre De Meyts, Waseem Sajid, Jane Palsgaard, Anne-Mette Theede, Lisbeth Gauguin, Hassan Aladdin, Jonathan Whittaker and Jonathan Whittaker

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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 £ subunits and two transmembrane £] subunits containing the tyrosine kinase domains. The £ 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 £ 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.

Pierre De Meyts
NIH/NIMH

Waseem Sajid

Jane Palsgaard

Anne-Mette Theede

Lisbeth Gauguin

Hassan Aladdin

Jonathan Whittaker

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Insulin and IGF-I Receptor Structure and Binding Mechanism

Pierre De Meyts, Waseem Sajid, Jane Palsgaard, Anne-Mette Theede, Lisbeth Gauguin, Hassan Aladdin, Jonathan Whittaker and Jonathan Whittaker

Chapter category: Endocrine

Insulin and IGF-I Receptor Structure and Binding Mechanism

Additional chapters from this book:

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