title: Structural Congruency of Ligand Binding to the Insulin and Insulin/Type 1 Insulin-like Growth Factor Hybrid Receptors.
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 α-chain C-terminal segment (αCT) 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 αCT peptide bound to an IR L1 plus cysteine-rich domain construct (IR310.T). These structures, refined at 3.0-Å 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.
authors.affiliation: Structural Biology Division, Walter and Eliza Hall Institute of Medical Research, Parkville, VIC 3052, Australia.
authors.forename: John G
authors.initials: JG
authors.lastname: Menting
authors.affiliation: Structural Biology Division, Walter and Eliza Hall Institute of Medical Research, Parkville, VIC 3052, Australia; Department of Medical Biology, University of Melbourne, Melbourne, VIC 3010, Australia.
authors.forename: Callum F
authors.initials: CF
authors.lastname: Lawrence
authors.affiliation: Structural Biology Division, Walter and Eliza Hall Institute of Medical Research, Parkville, VIC 3052, Australia.
authors.forename: Geoffrey K-W
authors.initials: GK
authors.lastname: Kong
authors.affiliation: Structural Biology Division, Walter and Eliza Hall Institute of Medical Research, Parkville, VIC 3052, Australia.
authors.forename: Mai B
authors.initials: MB
authors.lastname: Margetts
authors.affiliation: Structural Biology Division, Walter and Eliza Hall Institute of Medical Research, Parkville, VIC 3052, Australia.
authors.forename: Colin W
authors.initials: CW
authors.lastname: Ward
authors.affiliation: Structural Biology Division, Walter and Eliza Hall Institute of Medical Research, Parkville, VIC 3052, Australia; Department of Medical Biology, University of Melbourne, Melbourne, VIC 3010, Australia. Electronic address: lawrence@wehi.edu.au.
authors.forename: Michael C
authors.initials: MC
authors.lastname: Lawrence
mesh_terms: D001665:Binding Sites; D018360:Crystallography, X-Ray; D006801:Humans; D007334:Insulin-Like Growth Factor I / Q000737:chemistry*; D008024:Ligands; D008958:Models, Molecular; D011485:Protein Binding; D020836:Protein Structure, Quaternary; D017433:Protein Structure, Secondary; D017526:Receptor, IGF Type 1 / Q000737:chemistry*; D011972:Receptor, Insulin / Q000737:chemistry*
chemical_list: D008024:Ligands; D007334:Insulin-Like Growth Factor I; D017526:Receptor, IGF Type 1; D011972:Receptor, Insulin