Evolution of the macroglobulin protein family: from bacteria to primates

Proteins of the macroglobulin family are thioether-containing glycoproteins that act as inhibitors of a wide range of hydrolases, transporters and regulators of cytokine, hormone, lipid and oligonucleotide synthesis. As ancient components of innate immunity, these proteins are involved in folding of endogenous proteins as well as recognition and presentation of exogenous antigens. Interaction of macroglobulins with transmembrane receptors triggers cascades of reactions that regulate energy metabolism, cell division and apoptosis, participate in reproduction and cancerogenesis. A broad spectrum of conformational and functional states of molecules, depending on the type of ligands, and an appropriate set of implemented functions allow us to consider these proteins as key regulators of proteostasis. This review addresses the structure and function of macroglobulin proteins during evolution of organisms staying at different phylogenetic levels.