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Chapitre D'ouvrage Année : 2017

Structural and functional diversity of snake sarafotoxins

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Résumé

Sarafotoxins (SRTXs) are extracted solely from the venom of snakes belonging to the Atractaspis genus, a burrowing asp from Africa and Middle East. They share a high-sequence homology with endothelins, potent vasoconstrictors produced by mammalian endothelial cells and implicated in vascular tone regulation and cell growth. SRTXs and endothelins have a common core of 21 amino acids and two conserved disulfide bridges between cysteines +1/+15 and +3/+11 which constitute a unique and typical ``signature'' among natural bioactive peptides: Cys$_1$-XCys$_3$... Cys$_{11}$-X-X-X-Cys$_{15}$. SRTXs bind to endothelin receptors ET-A and ET-B situated on the membrane of numerous cells especially endothelial cells and smooth muscle cells. Recently long SRTXs have been discovered in the venom of A. microlepidota microlepidota and A. irregularis. These long SRTXs have three or four additional amino acids on their C-terminal domain. The affinity of long SRTXs for endothelin receptors is dramatically decreased compared to short SRTXs. Nevertheless, they still have a high toxicity as tested on mice. Combining invasive and echocardiographic procedures, recent experiments showed that short and long SRTXs have very different in vivo hemodynamic effects. Short SRTXs impair left ventricular function while long SRTXs impair right ventricular function and increase airway pressures with no effect on left ventricular function. Further experiments are needed to explain this discrepancy. The hypotheses of a new type of endothelin receptors (non-A non-B) cannot be discarded. Thus, the C-terminus extension seems to play a major role in defining the in vivo effect of these peptides.
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Dates et versions

hal-03575524 , version 1 (15-02-2022)

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Yazine Mahjoub, Stephanie Malaquin, Frederic Ducancel. Structural and functional diversity of snake sarafotoxins. P. Gopalakrishnakone (Editor-in-Chief); Hidetoshi Inagaki; Carl-Wilhelm Vogel; Ashis K. Mukherjee; Tarek R. Rahmy. Snake venoms, , pp.253-264, 2017, Toxinology book series (Toxi), 978-94-007-6410-1; 978-94-007-6409-5. ⟨10.1007/978-94-007-6648-8_1-1⟩. ⟨hal-03575524⟩
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