7S0Q

Head region of a complex of IGF-I with the ectodomain of a hybrid insulin receptor / type 1 insulin-like growth factor receptor

Summary for 7S0Q

• Entry DOI: 10.2210/pdb7s0q/pdb
• EMDB information: 24791
• Descriptor: Insulin-like growth factor 1 receptor, Insulin receptor, Insulin-like growth factor I, ... (7 entities in total)
• Functional Keywords: insulin receptor, type 1 insulin like growth factor receptor, hybrid receptor, insulin like growth factor i, leucine zipper, cryo electron microscopy, signaling protein
• Biological source: Homo sapiens (Human); More
• Total number of polymer chains: 3
• Total formula weight: 229736.71

Authors

Xu, Y.,Lawrence, M.C. (deposition date: 2021-08-30, release date: 2022-07-06, Last modification date: 2024-10-23)

Primary citation

Xu, Y.,Margetts, M.B.,Venugopal, H.,Menting, J.G.,Kirk, N.S.,Croll, T.I.,Delaine, C.,Forbes, B.E.,Lawrence, M.C.
How insulin-like growth factor I binds to a hybrid insulin receptor type 1 insulin-like growth factor receptor.
Structure, 30:1098-1108.e6, 2022

PubMed Abstract: Monomers of the insulin receptor and type 1 insulin-like growth factor receptor (IGF-1R) can combine stochastically to form heterodimeric hybrid receptors. These hybrid receptors display ligand binding and signaling properties that differ from those of the homodimeric receptors. Here, we describe the cryoelectron microscopy structure of such a hybrid receptor in complex with insulin-like growth factor I (IGF-I). The structure (ca. 3.7 Å resolution) displays a single IGF-I ligand, bound in a similar fashion to that seen for IGFs in complex with IGF-1R. The IGF-I ligand engages the first leucine-rich-repeat domain and cysteine-rich region of the IGF-1R monomer (rather than those of the insulin receptor monomer), consistent with the determinants for IGF binding residing in the IGF-1R cysteine-rich region. The structure broadens our understanding of this receptor family and assists in delineating the key structural motifs involved in binding their respective ligands.

PubMed: 35660159
DOI: 10.1016/j.str.2022.05.007

Experimental method

ELECTRON MICROSCOPY (3.7 Å)