A MODEL FOR INSULIN BINDING TO THE INSULIN-RECEPTOR

被引:199
作者
SCHAFFER, L
机构
[1] Insulin Research, Novo Nordisk A/S, Bagsværd
来源
EUROPEAN JOURNAL OF BIOCHEMISTRY | 1994年 / 221卷 / 03期
关键词
D O I
10.1111/j.1432-1033.1994.tb18833.x
中图分类号
Q5 [生物化学]; Q7 [分子生物学];
学科分类号
071010 ; 081704 ;
摘要
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 alpha 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 alpha 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.
引用
收藏
页码:1127 / 1132
页数:6
相关论文
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