Chironex fleckeri ( Box Jellyfish) Venom Proteins EXPANSION OF A CNIDARIAN TOXIN FAMILY THAT ELICITS VARIABLE CYTOLYTIC AND CARDIOVASCULAR EFFECTS*

被引:60
|
作者
Brinkman, Diane L. [1 ]
Konstantakopoulos, Nicki [2 ]
McInerney, Bernie V. [3 ]
Mulvenna, Jason [4 ]
Seymour, Jamie E. [5 ]
Isbister, Geoffrey K. [2 ,6 ]
Hodgson, Wayne C. [2 ]
机构
[1] Townsville Mail Ctr, Australian Inst Marine Sci, Townsville, Qld 4810, Australia
[2] Monash Univ, Dept Pharmacol, Monash Venom Grp, Melbourne, Vic 3800, Australia
[3] Macquarie Univ, Australian Proteome Anal Facil, Sydney, NSW 2109, Australia
[4] QIMR Berghofer Med Res Inst, Brisbane, Qld 4006, Australia
[5] James Cook Univ, Fac Med Hlth & Mol Sci, Cairns 4870, Australia
[6] Univ Newcastle, Sch Med & Publ Hlth, Newcastle, NSW 2308, Australia
基金
英国医学研究理事会;
关键词
Bioinformatics; Cardiovascular; Endotoxin; Protein Purification; Toxins; Cubozoa; Cytolytic; Jellyfish Toxin; Nematocyst; Venom; BACILLUS-THURINGIENSIS; PARTIAL-PURIFICATION; SEA WASP; MOLECULAR CHARACTERIZATION; INSECTICIDAL TOXIN; CRYSTAL-STRUCTURE; DELTA-ENDOTOXIN; CARYBDEA-ALATA; HABU-KURAGE; PREDICTION;
D O I
10.1074/jbc.M113.534149
中图分类号
Q5 [生物化学]; Q7 [分子生物学];
学科分类号
071010 ; 081704 ;
摘要
Background: Box jellyfish produce a unique family of toxic venom proteins. Results: The toxins are structurally similar, yet two subgroups confer different cytolytic activities in red blood cells and cardiovascular effects in rats. Conclusion: Diversification within the toxin family may influence toxin function/specificity. Significance: Characterization of the toxins provides new insight into their potential roles in human envenoming. The box jellyfish Chironex fleckeri produces extremely potent and rapid-acting venom that is harmful to humans and lethal to prey. Here, we describe the characterization of two C. fleckeri venom proteins, CfTX-A (approximate to 40 kDa) and CfTX-B (approximate to 42 kDa), which were isolated from C. fleckeri venom using size exclusion chromatography and cation exchange chromatography. Full-length cDNA sequences encoding CfTX-A and -B and a third putative toxin, CfTX-Bt, were subsequently retrieved from a C. fleckeri tentacle cDNA library. Bioinformatic analyses revealed that the new toxins belong to a small family of potent cnidarian pore-forming toxins that includes two other C. fleckeri toxins, CfTX-1 and CfTX-2. Phylogenetic inferences from amino acid sequences of the toxin family grouped CfTX-A, -B, and -Bt in a separate clade from CfTX-1 and -2, suggesting that the C. fleckeri toxins have diversified structurally and functionally during evolution. Comparative bioactivity assays revealed that CfTX-1/2 (25 g kg(-1)) caused profound effects on the cardiovascular system of anesthetized rats, whereas CfTX-A/B elicited only minor effects at the same dose. Conversely, the hemolytic activity of CfTX-A/B (HU50 = 5 ng ml(-1)) was at least 30 times greater than that of CfTX-1/2. Structural homology between the cubozoan toxins and insecticidal three-domain Cry toxins (-endotoxins) suggests that the toxins have a similar pore-forming mechanism of action involving -helices of the N-terminal domain, whereas structural diversification among toxin members may modulate target specificity. Expansion of the cnidarian toxin family therefore provides new insights into the evolutionary diversification of box jellyfish toxins from a structural and functional perspective.
引用
收藏
页码:4798 / 4812
页数:15
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