NMR structures of the micelle-bound polypeptide hormone glucagon

Abstract

The determination of the spatial structure of the polypeptide hormone glucagon bound to perdeuterated dodecylphosphocholine (DPC) micelles was the first attempt to apply two-dimensional (2D) NMR methods to a biologically relevant problem. The glucagon–DPC complex had considerably higher molecular weight than any other molecule investigated by 2D NMR at the time. Nevertheless, almost complete proton resonance assignments could be obtained. The structure determination was not only a challenge for the newly developed 2D NMR methodology, but also for the computers on which the structures were calculated. Micelle-bound glucagon did not adopt a globular tertiary structure; it contained well-defined structured parts, as well as flexible sections. The overall spatial arrangement of the polypeptide chain was largely determined by the topology of the lipid support. The results obtained with the glucagon–DPC system were an essential breakthrough demonstrating the superiority of 2D NMR methods. Copyright © 2003 John Wiley & Sons, Ltd.