Antioxidant evolution of fibrinogen: a crucial role of methionines

This review aims to provide evidence that the fibrinogen-like structures of invertebrates (on the example of the intracellular coagulation protein coagulogen from horseshoe crabs) and fibrinogen of vertebrates (such as lampreys, which are among the most primitive extant vertebrates, as well as higher-ordered animals on the phylogenetic evolutionary scale, such as chickens and humans) reflect their methionine-dependent adaptation to the steady-state level of reactive oxygen species (ROS). Since methionine residues disposed in primary structure of proteins may serve as ROS interceptors, the absence of methionines in the coagulogen structure suggests that it is not subject to ROS attack in the same extent as vertebrate extracellular fibrinogen. The structures of vertebrate fibrinogens (such as the central E-nodule composed of the NH₂-terminal portions of all six chains of the fibrinogen molecule, β-, and γ-nodules consisting of the C-terminal parts of the β and γ chains, respectively, and α-helical coiled-coil connectors, which hold the central and distal nodules of fibrinogen together) have minor differences among distant species. With the exception of the E-nodule, each of these conserved, homologous structures of vertebrate fibrinogens exhibits a similar distribution of methionines, including surface-exposed ones. It is suggested that the structures of the variable αC regions evolved to enhance their role in not only the fibrin assembly process but also the antioxidant protection of the central E-nodule. This implies that evolutionary processes of fibrinogen structure in different species and methionine-dependent defense are intrinsically linked.