Insulinand its receptor: structure, function and evolution

被引:242
作者
De Meyts, P [1 ]
机构
[1] Hagedorn Res Inst, Receptor Biol Lab, DK-2820 Gentofte, Denmark
关键词
D O I
10.1002/bies.20151
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
I present here a personal perspective on more than three decades of research into the structural biology of the insulin-receptor interaction. The solution of the three-dimensional structure of insulin in 1969 provided a detailed understanding of the insulin surfaces involved in self-assembly. In subsequent years, hundreds of insulin analogues were prepared by insulin chemists and molecular biologists, with the goal of relating the structure to the biological function of the molecule. The design of methods for direct receptor-binding studies in the 1970s, and the cloning of the receptor in the mid 1980s, provided the required tools for detailed structure-function studies. In the absence of a full three-dimensional structure of the insulin-receptor complex, I attempt to assemble the existing pieces of the puzzle generated by our and other laboratories, in order to generate a plausible mechanistic model of the insulin-receptor interaction that explains its kinetics and negative cooperativity. (C) 2004 Wiley Periodicals, Inc.
引用
收藏
页码:1351 / 1362
页数:12
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