EMD-24927
Leg region of a complex of IGF-I with the ectodomain of a hybrid insulin receptor / type 1 insulin-like growth factor receptor
EMD-24927
Single-particle3.73 Å
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Map released: 06/07/2022
Last modified: 23/10/2024
Sample Organism:
Homo sapiens
Sample: a complex of IGF-I with the ectodomain of a hybrid insulin receptor / type 1 insulin-like growth factor receptor
Fitted models: 7s8v (Avg. Q-score: 0.232)
Deposition Authors: Xu Y, Lawrence MC
Sample: a complex of IGF-I with the ectodomain of a hybrid insulin receptor / type 1 insulin-like growth factor receptor
Fitted models: 7s8v (Avg. Q-score: 0.232)
Deposition Authors: Xu Y, Lawrence MC
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How insulin-like growth factor I binds to a hybrid insulin receptor type 1 insulin-like growth factor receptor.
Xu Y,
Margetts MB,
Venugopal H
,
Menting JG,
Kirk NS
,
Croll TI,
Delaine C,
Forbes BE
,
Lawrence MC
(2022) Structure , 30 , 1098 - 1108.e6
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(2022) Structure , 30 , 1098 - 1108.e6
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.
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.