Properties of the Insulin Receptor Ectodomain

Overview

Journal Proc Natl Acad Sci U S A

Specialty Science

Date 1988 Oct 1

PMID 3050997

Citations 15

Authors

J D Johnson

M L Wong

W J Rutter

Affiliations

Soon will be listed here.

Abstract

To study the properties of the extracellular insulin-binding domain of the human insulin receptor (hIR), we have expressed portions of the parent molecule in mammalian cells. Receptor cDNAs encoding the entire hIR ectodomain, the alpha subunit of the hIR alone, or a portion of the alpha subunit containing the cysteine-rich region were placed within an expression vector and in turn used to transfect CHO cells. Only cells expressing mRNA for the entire hIR ectodomain secreted hIR-related protein, suggesting that the truncated versions of this domain are unstable. The ectodomain molecules were extensively glycosylated, properly processed heterotetramers. Further, they bound insulin with an affinity similar to that of the intact hIR. In the electron microscope the secreted ectodomains appeared as discrete globular structures. After incubation with roughly equimolar quantities of insulin, the ectodomains associated to form loops or branched and folded linear macroarrays. However, these structures were not restricted to the specific ligand, insulin, since epidermal growth factor also produced the effect. Nevertheless, it seems that the receptor ectodomains can exist in two structural states. The conversion of the singular to the aggregated state may somehow be associated with transmembrane communication and activation of the biological response.

Citing Articles

Structure of the insulin receptor-insulin complex by single-particle cryo-EM analysis.

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Hormone-triggered conformational changes within the insulin-receptor ectodomain: requirement for transmembrane anchors.

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Epidermal growth factor binding induces a conformational change in the external domain of its receptor.

Greenfield C, Hiles I, Waterfield M, Federwisch M, Wollmer A, Blundell T EMBO J. 1989; 8(13):4115-23.

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