1i02

Structural highlights

Function

3SA3_NAJAT Basic protein that binds to cell membrane and depolarizes cardiomyocytes. This cytotoxin also possesses lytic activity on many other cells, including red blood cells (PubMed:8182052). Interaction with sulfatides in the cell membrane induces pore formation and cell internalization. Cytotoxicity is due to pore formation, and to another mechanism independent of membrane-damaging activity. When internalized, it targets the mitochondrial membrane and induces mitochondrial swelling and fragmentation. It inhibits protein kinases C. It binds to the integrin alpha-V/beta-3 (ITGAV/ITGB3) with a moderate affinity (PubMed:16407244). It also binds with high affinity to heparin (PubMed:17685633).^{[1] [2] [3] [4] [5] [6] [7]}

Evolutionary Conservation

Check, as determined by ConSurfDB. You may read the explanation of the method and the full data available from ConSurf.

See Also

• Cardiotoxin 3D structures

References

1. ↑ Wang CH, Wu WG. Amphiphilic beta-sheet cobra cardiotoxin targets mitochondria and disrupts its network. FEBS Lett. 2005 Jun 6;579(14):3169-74. PMID:15922335 doi:http://dx.doi.org/S0014-5793(05)00579-X
2. ↑ Wang CH, Liu JH, Lee SC, Hsiao CD, Wu WG. 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. 2006 Jan 6;281(1):656-67. Epub 2005 Nov 1. PMID:16263708 doi:10.1074/jbc.M507880200
3. ↑ Wu PL, Lee SC, Chuang CC, Mori S, Akakura N, Wu WG, Takada Y. Non-cytotoxic cobra cardiotoxin A5 binds to alpha(v)beta3 integrin and inhibits bone resorption. Identification of cardiotoxins as non-RGD integrin-binding proteins of the Ly-6 family. J Biol Chem. 2006 Mar 24;281(12):7937-45. Epub 2006 Jan 10. PMID:16407244 doi:http://dx.doi.org/M513035200
4. ↑ Chen KC, Kao PH, Lin SR, Chang LS. The mechanism of cytotoxicity by Naja naja atra cardiotoxin 3 is physically distant from its membrane-damaging effect. Toxicon. 2007 Nov;50(6):816-24. Epub 2007 Jun 27. PMID:17714752 doi:http://dx.doi.org/S0041-0101(07)00224-3
5. ↑ Chien KY, Chiang CM, Hseu YC, Vyas AA, Rule GS, Wu W. Two distinct types of cardiotoxin as revealed by the structure and activity relationship of their interaction with zwitterionic phospholipid dispersions. J Biol Chem. 1994 May 20;269(20):14473-83. PMID:8182052
6. ↑ Chiou SH, Raynor RL, Zheng B, Chambers TC, Kuo JF. Cobra venom cardiotoxin (cytotoxin) isoforms and neurotoxin: comparative potency of protein kinase C inhibition and cancer cell cytotoxicity and modes of enzyme inhibition. Biochemistry. 1993 Mar 2;32(8):2062-7. PMID:8448165
7. ↑ Sue SC, Rajan PK, Chen TS, Hsieh CH, Wu W. Action of Taiwan cobra cardiotoxin on membranes: binding modes of a beta-sheet polypeptide with phosphatidylcholine bilayers. Biochemistry. 1997 Aug 12;36(32):9826-36. PMID:9245415 doi:http://dx.doi.org/10.1021/bi970413l