Abstract
The family of thioester-containing proteins (TEPs) appeared early in evolution: members of this family have been found in such diverse organisms as nematodes, insects, molluscs, fish, birds, and mammals (1). They are characterized by homologous sequence features, including a unique intrachain β-cysteinyl-γ-glutamyl thioester, and a propensity for multiple conformationally sensitive binding interactions (2). The presence of the highly reactive thioester bond renders the molecules unstable at elevated temperature and results in their autocatalytic fragmentation at the thioester site (3,4). Moreover, when exposed, the thioester bond is readily hydrolyzed by water. To avoid precocious inactivation, the thioester in the native protein is protected by a shielded environment (5,6). Proteolytic cleavage exposes a previously hidden thioester bond, which mediates covalent attachment through transacylation (7). The reactivity associated with the thioester is one of the defining features of this protein family. Another important feature is the propensity for diverse conformationally sensitive interactions with other molecules. This includes covalent attachment to activating self and nonself surfaces (complement factors), covalent or noncovalent crosslinking to the attacking proteases [α2-macroglobulins (α2Ms)], interactions with receptors (complement factors and α2Ms), and binding of cleavage-generated products to corresponding receptors (anaphylatoxins of complement factors). In addition, α2Ms bind cytokines and growth factors and regulate their clearance and activity (8,9).
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Levashina, E.A., Blandin, S., Moita, L.F., Lagueux, M., Kafatos, F.C. (2003). Thioester-Containing Proteins of Protostomes. In: Ezekowitz, R.A.B., Hoffmann, J.A. (eds) Innate Immunity. Infectious Disease. Humana Press, Totowa, NJ. https://doi.org/10.1007/978-1-59259-320-0_9
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