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.
Mancheño
J M
JM
Departamento de Bioquímica y Biología Molecular, Facultad de Química, Universidad Complutense, Madrid, Spain.
Gasset
M
M
Lacadena
J
J
Martínez del Pozo
A
A
Oñaderra
M
M
Gavilanes
J G
JG
D000595:Amino Acid Sequence; D000970:Antineoplastic Agents / Q000737:chemistry*; D001230:Aspergillus; D002462:Cell Membrane / Q000378:metabolism; D004722:Endoribonucleases; D005656:Fungal Proteins / Q000737:chemistry* / Q000378:metabolism; D008957:Models, Genetic; D008969:Molecular Sequence Data; D011487:Protein Conformation; D011500:Protein Synthesis Inhibitors / Q000737:chemistry*; D012260:Ribonucleases / Q000235:genetics
D000970:Antineoplastic Agents; D005656:Fungal Proteins; D011500:Protein Synthesis Inhibitors; C014801:alpha-sarcin; D004722:Endoribonucleases; D012260:Ribonucleases