How insulin-like growth factor I binds to a hybrid insulin receptor type 1 insulin-like growth factor receptor.
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Authors
Xu, Yibin
Margetts, Mai B
Venugopal, Hari
Menting, John G
Kirk, Nicholas S
Croll, Tristan I
Delaine, Carlie
Forbes, Briony E
Lawrence, Michael C
Publication Date
2022-08-04Journal Title
Structure
ISSN
0969-2126
Publisher
Elsevier BV
Type
Article
This Version
AM
Metadata
Show full item recordCitation
Xu, Y., Margetts, M. B., Venugopal, H., Menting, J. G., Kirk, N. S., Croll, T. I., Delaine, C., et al. (2022). How insulin-like growth factor I binds to a hybrid insulin receptor type 1 insulin-like growth factor receptor.. Structure https://doi.org/10.1016/j.str.2022.05.007
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.
Sponsorship
Wellcome Trust (082961/Z/07/A)
Wellcome Trust (209407/Z/17/Z)
Identifiers
External DOI: https://doi.org/10.1016/j.str.2022.05.007
This record's URL: https://www.repository.cam.ac.uk/handle/1810/336530
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