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TitleHow insulin-like growth factor I binds to a hybrid insulin receptor type 1 insulin-like growth factor receptor.
Journal, issue, pagesStructure, Vol. 30, Issue 8, Page 1098-11108.e6, Year 2022
Publish dateAug 4, 2022
AuthorsYibin Xu / Mai B Margetts / Hari Venugopal / John G Menting / Nicholas S Kirk / Tristan I Croll / Carlie Delaine / Briony E Forbes / Michael C Lawrence /
PubMed AbstractMonomers 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 ...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.
External linksStructure / PubMed:35660159 / PubMed Central
MethodsEM (single particle)
Resolution3.7 - 3.73 Å
Structure data

EMDB-24791, PDB-7s0q:
Head region of a complex of IGF-I with the ectodomain of a hybrid insulin receptor / type 1 insulin-like growth factor receptor
Method: EM (single particle) / Resolution: 3.7 Å

EMDB-24927, PDB-7s8v:
Leg region of a complex of IGF-I with the ectodomain of a hybrid insulin receptor / type 1 insulin-like growth factor receptor
Method: EM (single particle) / Resolution: 3.73 Å

Chemicals

ChemComp-BMA:
beta-D-mannopyranose / Mannose

ChemComp-NAG:
2-acetamido-2-deoxy-beta-D-glucopyranose / N-Acetylglucosamine

Source
  • homo sapiens (human)
KeywordsSIGNALING PROTEIN / insulin receptor / type 1 insulin like growth factor receptor / hybrid receptor / insulin like growth factor I / leucine zipper / cryo electron microscopy

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