Ligand-induced activation of the insulin receptor: a multi-step process involving structural changes in both the ligand and the receptor
- Author(s)
- Ward, CW; Lawrence, MC;
- Details
- Publication Year 2009-04,Volume 31,Issue #4,Page 422-434
- Journal Title
- BIOESSAYS
- Publication Type
- Journal Article
- Abstract
- Current models of insulin binding to the insulin receptor (IR) propose (i) that there are two binding sites on the surface of insulin which engage with two binding sites on the receptor and (ii) that ligand binding involves structural changes in both the ligand and the receptor. Many of the features of insulin binding to its receptor, namely B-chain helix interactions with the leucine-rich repeat domain and A-chain residue interactions with peptide loops from another part of the receptor, are also seen in models of relaxin and insulin-like peptide 3 binding to their receptors. We show that these principles can likely be extended to the group of mimetic peptides described by Schaffer and coworkers, which are reported to have no sequence identity with insulin. This review summarizes our current understanding of ligand-induced activation of the IR and highlights the key issues that remain to be addressed.
- Publisher
- JOHN WILEY & SONS INC
- Keywords
- GROWTH-FACTOR-I; ALANINE-SCANNING MUTAGENESIS; PHOTO-CROSS-LINKING; DIABETES-ASSOCIATED MUTATIONS; FAMILY PEPTIDE RECEPTORS; CHAIN ALPHA-HELIX; 1ST 3 DOMAINS; CRYSTAL-STRUCTURE; HIGH-AFFINITY; TYROSINE KINASE
- Publisher's Version
- https://doi.org/10.1002/bies200800210
- Terms of Use/Rights Notice
- Refer to copyright notice on published article.
Creation Date: 2009-04-01 12:00:00