How IGF-II Binds to the Human Type 1 Insulin-like Growth Factor Receptor

Human type 1 insulin-like growth factor receptor (IGF-1R) signals chiefly in response to the binding of insulin-like growth factor I. Relatively little is known about the role of insulin-like growth factor II signaling via IGF-1R, despite the affinity of insulin-like growth factor II for IGF-1R bein...

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Detalles Bibliográficos
Autores principales: Xu, Yibin, Kirk, Nicholas S., Venugopal, Hariprasad, Margetts, Mai B., Croll, Tristan I., Sandow, Jarrod J., Webb, Andrew I., Delaine, Carlie A., Forbes, Briony E., Lawrence, Michael C.
Formato: Online Artículo Texto
Lenguaje:English
Publicado: Cell Press 2020
Materias:
Article
Acceso en línea:https://www.ncbi.nlm.nih.gov/pmc/articles/PMC7343240/
https://www.ncbi.nlm.nih.gov/pubmed/32459985
http://dx.doi.org/10.1016/j.str.2020.05.002
Descripción
Sumario:Human type 1 insulin-like growth factor receptor (IGF-1R) signals chiefly in response to the binding of insulin-like growth factor I. Relatively little is known about the role of insulin-like growth factor II signaling via IGF-1R, despite the affinity of insulin-like growth factor II for IGF-1R being within an order of magnitude of that of insulin-like growth factor I. Here, we describe the cryoelectron microscopy structure of insulin-like growth factor II bound to a leucine-zipper-stabilized IGF-1R ectodomain, determined in two conformations to a maximum average resolution of 3.2 Å. The two conformations differ in the relative separation of their respective points of membrane entry, and comparison with the structure of insulin-like growth factor I bound to IGF-1R reveals long-suspected differences in the way in which the critical C domain of the respective growth factors interact with IGF-1R.

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