Abstract
The biological activity of glucagon is mediated through binding, with high affinity and specificity, to a membrane receptor, implying extensive and well-defined inter-molecular interactions (see Chap. 13). However, in dilute aqueous solutions glucagon has little defined secondary structure and almost certainly exists as a population of conformers in equilibrium. The formation of the receptor-hormone complex must involve either selection of one conformer from the population or induction of a conformer as the interaction takes place. Whatever the mechanism, the definition of the receptor-bound conformer, as well as the nature of the hormone- receptor interactions must be a primary objective in the understanding of the biology of glucagon and the design of glucagon agonists and inhibitors (Blundell 1979; Blundell and Humbel 1980). Unfortunately, the receptor has yet to be defined biochemically and so difect study of the receptor-hormone complex is not possible at present. Instead we must examine the conformation of glucagon in aqueous solution, in crystals, in lipid micelles and other environments in order to establish the nature of the conformational dependence on intermolecular interactions. Here, I first describe recent developments, especially in the use of X-ray diffraction and proton nuclear magnetic resonance (NMR) spectroscopy which have allowed description of the conformation in great detail under varied conditions. I then discuss the relevance of these conformations to the molecular biology of glucagon.
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© 1983 Springer-Verlag Berlin Heidelberg
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Blundell, T.L. (1983). The Conformation of Glucagon. In: Lefèbvre, P.J. (eds) Glucagon I. Handbook of Experimental Pharmacology, vol 66 / 1. Springer, Berlin, Heidelberg. https://doi.org/10.1007/978-3-642-68866-9_3
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DOI: https://doi.org/10.1007/978-3-642-68866-9_3
Publisher Name: Springer, Berlin, Heidelberg
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