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

ABSTRACT: 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.

SUBMITTER: Xu Y 

PROVIDER: S-EPMC7343240 | biostudies-literature | 2020 Jul

REPOSITORIES: biostudies-literature

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

Xu Yibin Y   Kirk Nicholas S NS   Venugopal Hariprasad H   Margetts Mai B MB   Croll Tristan I TI   Sandow Jarrod J JJ   Webb Andrew I AI   Delaine Carlie A CA   Forbes Briony E BE   Lawrence Michael C MC  

Structure (London, England : 1993) 20200526 7

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 IG  ...[more]

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