Predictive study of the conformation of the cytotoxic protein alpha-sarcin: a structural model to explain alpha-sarcin-membrane interaction.

Alpha-sarcin is a cytotoxic protein composed of a single polypeptide chain. This protein shows a significant degree of amino acid sequence similarity with a group of several phylogenetically related fungal ribonucleases. The leading member of such a group is ribonuclease T1. Three proteins of this group, ribonucleases T1, Ms and F1, are well known in terms of their crystal structures. These data have been used to propose a conformation for alpha-sarcin. The secondary structure of the cytotoxin would contain one alpha-helix segment as well as around six beta-strands and 14 beta-turns. The folding of these structural motifs is proposed by comparison with the three-dimensional structure of the three proteins from the ribonuclease T1 subfamily. The four longest beta-strands of alpha-sarcin would define an antiparallel beta-sheet structure resulting in a highly hydrophobic domain. The predicted folding for alpha-sarcin is discussed in terms of the ability of this protein to electrostatically and hydrophobically interact with phospholipid vesicles. The proposed conformation would explain how a highly polar protein, such as alpha-sarcin, can produce membrane destabilization resulting in protein translocation across lipid bilayers.