TCDB is operated by the Saier Lab Bioinformatics Group

1.C.74 The Snake Cytotoxin (SCT) Family

The Snake Cytotoxin (SCT) (the SwissProt Snake Toxin) Family is a huge family of cytotoxins produced in the venomous glands of various snakes. These proteins are usually 80-100 residues long and have a single N-terminal TMS. Cobra cardiotoxins induce membrane leakage and cell death. CTXA3 is the major cardiotoxin from Taiwan cobra venom. It is internalized into mitochondria. CTXA3 binds to sulfatides (sulfogalactosyl ceamides) in the plasma membrane and forms transmembrane beta-sheet pores. The structure of CTXA3 in complexation with sulfatides in a membrane-like environment has been solved to 2.3 Å resolution, and the mode of toxin insertion into the plasma membrane has been predicted (Wang et al., 2006). A lipid-mediated toxin translocation mechanism has been proposed (Wang et al., 2006). α-bungarotoxin, a homologue of cobra cardiotoxin, binds to and inhibits the acetylcholine receptor (TC #1.A.9). Its 3-dimensional structure is also known.

Sulfatides induce CTX A3 oligomerization in sulfatide containing phosphatidylcholine (PC) vesicles to form transient pores with pore size and lifetime in the range of about 30 A and 10-2 s, respectively (Tjong et al., 2007). Reorientation of sulfatide is needed for CTX A3 dimer formation.

The reaction catalyzed by transporting snake toxins is:

ions and small molecules (in) → ions and small molecules (out).

 

This family belongs to the: Aerolysin Superfamily.

References associated with 1.C.74 family:

Tjong, S.C., P.L. Wu, C.M Wang, W.N. Huang, N.L. Ho, and W.G. Wu. (2007). Role of glycosphingolipid conformational change in membrane pore forming activity of cobra cardiotoxin. Biochemistry. 46(43):12111-12123. 17918958
Wang, C.H., J.H. Liu, S.C. Lee, C.D. Hsiao, and W.G. Wu. (2006). Glycosphingolipid-facilitated membrane insertion and internalization of cobra cardiotoxin. The sulfatide·cardiotoxin complex structure in a membrane-like environment suggests a lipid-dependent cell-penetrating mechanism for membrane binding polypeptides. J. Biol. Chem. 281: 656-667. 16263708