Amphiphilic beta-sheet cobra cardiotoxin targets mitochondria and disrupts its network.
Recent advance in understanding the role of toxin proteins in controlling cell death has revealed that pro-apoptotic viral proteins targeting mitochondria contain amphiphilic alpha-helices with pore-forming properties. Herein, we describe that the pore-forming amphiphilic beta-sheet cardiotoxins (or cytotoxins, CTXs) from Taiwan cobra (Naja atra) also target mitochondrial membrane after internalization and act synergistically with CTX-induced cytosolic calcium increase to disrupt mitochondria network. It is suggested that CTX-induced fragmentation of mitochondria play a role in controlling CTX-induced necrosis of myocytes and cause severe tissue necrosis in the victims.
Wang
Chia-Hui
CH
Department of Life Sciences, Institute of Bioinformatics and Structural Biology, National Tsinghua University, 101, Section 2, Kuang Fu Road, Hsinchu 30013, Taiwan.
Wu
Wen-guey
WG
D000818:Animals; D002118:Calcium / Q000378:metabolism; D002460:Cell Line; D004179:Cobra Cardiotoxin Proteins / Q000737:chemistry* / Q000494:pharmacology*; D017815:Elapidae; D057927:Hydrophobic and Hydrophilic Interactions; D007425:Intracellular Membranes / Q000187:drug effects; D008929:Mitochondria, Heart / Q000187:drug effects* / Q000502:physiology*; D008958:Models, Molecular; D032446:Myoblasts / Q000187:drug effects / Q000473:pathology; D009336:Necrosis; D017433:Protein Structure, Secondary; D017434:Protein Structure, Tertiary; D051381:Rats; D014867:Water / Q000737:chemistry
D004179:Cobra Cardiotoxin Proteins; C082202:cardiotoxin III, Naja naja atra; D014867:Water; D002118:Calcium