The insulin receptor changes conformation in unforeseen ways on ligand binding: Sharpening the picture of insulin receptor activation.
- Author(s)
- Ward, CW; Menting, JG; Lawrence, MC;
- Details
- Publication Year 2013-11,Volume 35,Issue #11,Page 945-54
- Journal Title
- BioEssays
- Publication Type
- Journal Article
- Abstract
- Unraveling the molecular detail of insulin receptor activation has proved challenging, but a major advance is the recent determination of crystallographic structures of insulin in complex with its primary binding site on the receptor. The current model for insulin receptor activation is that two distinct surfaces of insulin monomer engage sequentially with two distinct binding sites on the extracellular surface of the insulin receptor, which is itself a disulfide-linked (αβ)2 homodimer. In the process, conformational changes occur both within the hormone and the receptor, the latter resulting in the disruption of the intracellular interactions that hold the kinase domains in their basal state and in the initiation of the phosphorylation events that drive insulin signaling. The purpose of this paper is to summarize the extant structural data relating to hormone binding and how it effects receptor activation, as well as to discuss the issues that remain unresolved.
- Publisher
- WILEY
- Keywords
- crystal structure ; insulin ; insulin-like growth factor ; insulin receptor ; negative cooperativity ; signaling mechanism ; type 1 insulin-like growth factor receptor
- Research Division(s)
- Structural Biology
- Publisher's Version
- https://doi.org/10.1002/bies.201300065
- NHMRC Grants
- NHMRC/1005896,
- Terms of Use/Rights Notice
- © 2013 WILEY Periodicals, Inc.
Creation Date: 2013-11-01 12:00:00
Last Modified: 2015-04-02 08:44:20