Structural congruency of ligand binding to the insulin and insulin/type 1 insulin-like growth factor hybrid receptors
- Author(s)
- Menting, JG; Lawrence, CF; Kong, GK; Margetts, MB; Ward, CW; Lawrence, MC;
- Details
- Publication Year 2015-07-07,Volume 23,Issue #7,Page 1271-82
- Journal Title
- Structure
- Publication Type
- Journal Article
- Abstract
- The homodimeric insulin and type 1 insulin-like growth factor receptors (IR and IGF-1R) share a common architecture and each can bind all three ligands within the family: insulin and insulin-like growth factors I and II (IGF-I and IFG-II). The receptor monomers also assemble as heterodimers, the primary ligand-binding sites of which each comprise the first leucine-rich repeat domain (L1) of one receptor type and an alpha-chain C-terminal segment (alphaCT) of the second receptor type. We present here crystal structures of IGF-I bound to such a hybrid primary binding site and of a ligand-free version of an IR alphaCT peptide bound to an IR L1 plus cysteine-rich domain construct (IR310.T). These structures, refined at 3.0-A resolution, prove congruent to respective existing structures of insulin-complexed IR310.T and the intact apo-IR ectodomain. As such, they provide key missing links in the emerging, but sparse, repertoire of structures defining the receptor family.
- Publisher
- Cell Press
- Research Division(s)
- Structural Biology
- PubMed ID
- 26027733
- Publisher's Version
- https://doi.org/10.1016/j.str.2015.04.016
- NHMRC Grants
- NHMRC/1005896, NHMRC/1058233,
- Terms of Use/Rights Notice
- Refer to copyright notice on published article.
Creation Date: 2015-06-15 09:53:28
Last Modified: 2015-07-14 02:51:49