ABSTRACT
Disintegrins represent a family of polypeptides released in the venoms of Viperidae (vipers and rattlesnakes) by the proteolytic processing of multidomain metalloproteinases, which selectively block the function of β1 and β3 integrin receptors. Research on disintegrins not only is relevant for understanding the evolution and biology of viper venom toxins, but also provides information of new structural determinants involved in integrin recognition that may be useful in both basic and clinical research. Here, we describe the application of proteomics (“snake venomics”) for the detailed characterization of the toxin content of snake venoms, and review our current view and hypotheses on the emergence and the structural and functional diversication of disintegrins by accelerated evolution and the minimization of the structure of both the duplicated genes (loss of intronic sequences) and the venom expressed proteins (selective loss of disulde bonds). The role of the composition, conformation, and concerted dynamics of the integrin inhibitory loop and the C-terminal tail in determining the selective inhibition of integrin receptors is discussed.
