Abstract: On the basis of analysis of own and literature data on insulin-receptor interaction two centers responsible for receptor binding were identified on 3D-structure of insulin with receptor. Two extracellular domains of insulin receptor interact with these centers on insulin molecule. The comparative analysis of primary structures of the protein disulfide isomerase thioredoxine domains and C-terminal domain of the receptor suggests existence of the thioredoxine domain in the insulin receptor. In this connection the role of the thiol disulfide an exchange reaction is discussed in terms of insulin interaction with receptor followed by subsequent conformational changes in the receptor molecule and activation of the intercellular tyrosine kinase domain.
It is supposed, that besides known mechanism of receptor mediated insulin signal transduction and tyrosine kinase activation, there is other mechanism of insulin intracellular signal transduction realised via cytosolic insulin-binding proteins. Major components of intercellular insulin signal transduction include: protein disulfide isomerase and insulin degrading enzyme. The importance of change of the intracellular insulin degradation rate for insulin signal transduction is discussed.
Reference: Prozorovskiy V.N., Lokhov P.G., Maslov D.L., Ipatova O.M., Structurally functional features of insulin and mechanism of its action, Biomeditsinskaya khimiya, 2003, vol: