Role of heparan sulfates and glycosphingolipids in the pore formation of basic polypeptides of cobra cardiotoxin.
Cobra venom contains cardiotoxins (CTXs) that induce tissue necrosis and systolic heart arrest in bitten victims. CTX-induced membrane pore formation is one of the major mechanisms responsible for the venom's designated cytotoxicity. This chapter examines how glycoconjugates such as heparan sulfates (HS) and glycosphingolipids, located respectively in the extracellular matrix and lipid bilayers of the cell membranes, facilitate CTX pore formation. Evidences for HS-facilitated cell surface retention and glycosphingolipid-facilitated membrane bilayer insertion of CTX are reviewed. We suggest that similar physical steps could play a role in the mediation of other pore forming toxins (PFT). The membrane pores formed by PFT are expected to have limited lifetime on biological cell surface as a result of membrane dynamics during endocytosis and/or rearrangement of lipid rafts.
Wu
Wen-Guey
WG
National Synchrotron Radiation Research Center and Department of Life Science, National Tsing Hua University, 101 Kuang Fu Road 2nd Sec, Hsinchu 30043, Taiwan. wgwu@life.nthu.edu.tw
Tjong
Siu-Cin
SC
Wu
Po-Long
PL
Kuo
Je-Hung
JH
Wu
Karen
K
D000818:Animals; D004179:Cobra Cardiotoxin Proteins / Q000737:chemistry* / Q000378:metabolism; D017815:Elapidae; D006323:Heart Arrest / Q000378:metabolism; D006497:Heparan Sulfate / Q000737:chemistry* / Q000378:metabolism; D006801:Humans; D008051:Lipid Bilayers / Q000737:chemistry* / Q000378:metabolism; D021962:Membrane Microdomains / Q000737:chemistry* / Q000378:metabolism; D009336:Necrosis / Q000378:metabolism; D052899:Pore Forming Cytotoxic Proteins / Q000737:chemistry* / Q000378:metabolism; D013107:Sphingolipids / Q000737:chemistry* / Q000378:metabolism
D004179:Cobra Cardiotoxin Proteins; D006497:Heparan Sulfate; D008051:Lipid Bilayers; D052899:Pore Forming Cytotoxic Proteins; D013107:Sphingolipids