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A model for insulin binding to the insulin receptor

A model for insulin binding to the insulin receptor The affinities of a number of insulin analogues for the human insulin receptor, a truncated soluble form of the insulin receptor, and the human insulin‐like growth factor 1 receptor were determined. Insulin analogues with substitutions in the A13 or B17 positions were shown to have anomalous binding properties. This suggests that these positions, which are located in the hexamer‐forming surface on the opposite side of the molecule from the classical binding site, constitute a second domain of the molecule important for receptor binding. In the present work, a model is proposed where each of the two α subunits of the insulin receptor contributes with a different binding region to the formation of the high‐affinity binding site. Subsequently, a second molecule of insulin is able to bind to a low‐affinity site involving only one of the α subunits, thus accounting for the curvilinear Scatchard plot. The affinity of the low‐affinity site could be estimated using a high‐affinity insulin analogue as the tracer. The model also provides the framework for a molecular explanation of the negative cooperativity phenomenon. http://www.deepdyve.com/assets/images/DeepDyve-Logo-lg.png The Febs Journal Wiley

A model for insulin binding to the insulin receptor

SCHÄFFER, Lauge
The Febs Journal , Volume 221 (3) – May 1, 1994
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References (38)

Publisher
Wiley
Copyright
Copyright © 1994 Wiley Subscription Services, Inc., A Wiley Company
ISSN
1742-464X
eISSN
1742-4658
DOI
10.1111/j.1432-1033.1994.tb18833.x
Publisher site
See Article on Publisher Site

Abstract

The affinities of a number of insulin analogues for the human insulin receptor, a truncated soluble form of the insulin receptor, and the human insulin‐like growth factor 1 receptor were determined. Insulin analogues with substitutions in the A13 or B17 positions were shown to have anomalous binding properties. This suggests that these positions, which are located in the hexamer‐forming surface on the opposite side of the molecule from the classical binding site, constitute a second domain of the molecule important for receptor binding. In the present work, a model is proposed where each of the two α subunits of the insulin receptor contributes with a different binding region to the formation of the high‐affinity binding site. Subsequently, a second molecule of insulin is able to bind to a low‐affinity site involving only one of the α subunits, thus accounting for the curvilinear Scatchard plot. The affinity of the low‐affinity site could be estimated using a high‐affinity insulin analogue as the tracer. The model also provides the framework for a molecular explanation of the negative cooperativity phenomenon.

Journal

The Febs Journal – Wiley

Published: May 1, 1994

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