How insulin-like growth factor I binds to a hybrid insulin receptor type 1 insulin-like growth factor receptor

Yibin Xu, Mai B. Margetts, Hari Venugopal, John G. Menting, Nicholas S. Kirk, Tristan I. Croll, Carlie Delaine, Briony E. Forbes, Michael C. Lawrence

Research output: Contribution to journalArticlepeer-review

4 Citations (Scopus)
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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.

Original languageEnglish
Pages (from-to)1098-1108.e6
Number of pages18
JournalSTRUCTURE
Volume30
Issue number8
Early online date3 Jun 2022
DOIs
Publication statusPublished - 4 Aug 2022

Keywords

  • cryo-electron microscopy
  • hybrid receptor
  • insulin receptor
  • insulin-like growth factor I
  • leucine zipper
  • type 1 insulin-like growth factor receptor

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