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

✍ Scribed by Jose M. Mancheño; Maria Gasset; Javier Lacadena; Alvaro Martı́nez del Pozo; Mercedes Oñaderra; Jose G. Gavilanes

• Publisher: Elsevier Science
• Year: 1995
• Tongue: English
• Weight: 694 KB
• Volume: 172
• Category: Article
• ISSN: 0022-5193
• DOI: 10.1006/jtbi.1995.0022

✦ Synopsis

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 a-sarcin. The secondary structure of the cytotoxin would contain one a-helix segment as well as around six b-strands and 14 b-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 b-strands of a-sarcin would define an antiparallel b-sheet structure resulting in a highly hydrophobic domain. The predicted folding for a-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 a-sarcin, can produce membrane destabilization resulting in protein translocation across lipid bilayers.