The Binding Ability of Insulin-Related Peptides as the Clue to the Search for Their Functional Role in Phylogenesis. Introduction to the Problem

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Abstract

The common plan of structure of the main peptides of the vertebrate insulin family—insulin itself, IGF-I, IGF-II, and relaxin—has distinct structural formations. Each of the peptides performs its characteristic function. However, overlapping of insulin and IGF-I actions and its stability in the vertebrate phylogenesis have formed the concept of their regulation of growth and metabolism as a function fixed in phylogenesis for a certain type of structures. At the same time, study of insulin-related peptides in invertebrates has revealed the wider spectrum, than in vertebrates, of biological effects; this indicated that the similarity of the total structure design is not sufficient for judging about their functional role. Functional possibilities of a regulatory peptide depend fundamentally on its capability for binding to the receptor realizing its biological action. However, the binding ability has a wider significance than merely transmission of biological signals. Thus, IGF-II when interacting with receptors realizing its biological effects also binds to the IGF-2 receptor limiting its action and, besides, to the binding proteins (BP) modulating its action. The entire cycle of interactions occurs in the body at different affinity levels. Meanwhile, insulin interacts neither with IGF-2 receptor nor with BP. In this case, specificity and sequence of interaction with each of receptors or with protein are due not to the general design of the peptide structure, but rather to structure of individual submolecular determinants—binding domains. The leading role in disclosure of composition and structure of these domains is played by the “mutant-ligand” approach evaluating affinity of modified analogs. To analyze role of structural elements of the binding domains, the author proposes the system of estimation of affinity of the studied analogs. The present work, alongside with consideration of methodical aspects of the forthcoming analysis, is an introduction to the problem of organization of the binding domains connected directly with functional role of peptides of the insulin type. The proposed analysis is due to necessity of specification of this organization both in one molecule and in different molecules with a similar plan of structure on the basis of not always unanimous literature data and of clarification of principles of structure of these domains.

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