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[Lipid-protein interactions and conformation of proteinaceous macromolecules]
1Department of Molecular Immunology, A. V. Palladin Institute of Biochemistry, Kyiv, Ukraine. sergiy@igc.gulbenkian.pt
Analysis of the data as to the mechanism of specific antibody transformation into polyreactive immunoglobulins (PRIG) shows that for this transformation it is necessary and sufficiently to deprive antibodies of lipids, which are in norm tightly bound to the antibodies. Removal of these lipids by any methods (by treatment of antibodies with chaotropic ions, low/high pH, reactive oxygen species and lipases) leads to the loose by antibodies of their specificity and acquiring the ability to react with various non-related antigens, i.e. to their conversion into PRIG. Mathematical modeling of the PRIG--antigen interaction and values of thermodynamic characteristics of this process shows that antigen-binding domains of PRIG are in semi-melted state, thanks to what they can fit their structure to be complementary to structurally different antigens. Thus, we conclude that lipids bound to the so-called "hydrophobic pockets" of immunoglobulins (Ig) can stabilize the conformation of Ig and increase their rigidity, and removal of these lipids induce flexibility of Ig domains, responsible for interaction with antigens. It was presumed that lipids could exert the similar function of conformation stabilization not only in the case of antibodies, but also combining with some other proteins, for example, enzymes. Their removal could lead to the changing of protein conformation and loosing its biological activity. In this case the function of lipid removing and protein inactivation could exert cellular reactive oxygen species and cellular lipases and lipoxygenases.
Analysis of the data as to the mechanism of specific antibody transformation into polyreactive immunoglobulins (PRIG) shows that for this transformation it is necessary and sufficiently to deprive antibodies of lipids, which are in norm tightly bound to the antibodies. Removal of these lipids by any methods (by treatment of antibodies with chaotropic ions, low/high pH, reactive oxygen species and lipases) leads to the loose by antibodies of their specificity and acquiring the ability to react with various non-related antigens, i.e. to their conversion into PRIG. Mathematical modeling of the PRIG--antigen interaction and values of thermodynamic characteristics of this process shows that antigen-binding domains of PRIG are in semi-melted state, thanks to what they can fit their structure to be complementary to structurally different antigens. Thus, we conclude that lipids bound to the so-called "hydrophobic pockets" of immunoglobulins (Ig) can stabilize the conformation of Ig and increase their rigidity, and removal of these lipids induce flexibility of Ig domains, responsible for interaction with antigens. It was presumed that lipids could exert the similar function of conformation stabilization not only in the case of antibodies, but also combining with some other proteins, for example, enzymes. Their removal could lead to the changing of protein conformation and loosing its biological activity. In this case the function of lipid removing and protein inactivation could exert cellular reactive oxygen species and cellular lipases and lipoxygenases.