March 2010

[JBC] A Novel Neurotoxin

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Biobits---Neurotoxin
Haditoxin subunit A (blue) superimposed on erabutoxin-a (magenta), erabutoxin-b (cyan) and toxin-α (green).

Snake venoms contain a rich cocktail of pharmacologically active peptides and proteins that have contributed greatly to scientific advances, such as understanding receptor activity and developing new therapeutics. The authors of this paper have now added another member to this class of valuable peptides, providing a detailed structural and functional characterization of a novel neurotoxin from the venom of the King cobra. Their 1.5-Å crystal structure revealed that this new toxin, called haditoxin, exists as a homodimer, similar to the k-neurotoxin family. Interestingly, however, the monomeric subunits of haditoxin, which consist of a three-finger protein fold, closely resemble short-chain α-neurotoxins, unlike k-neurotoxin monomers, which resemble long-chain α-neurotoxins. Perhaps more interestingly, while haditoxin could antagonize several classes of nicotinic acetylcholine receptors (nAChRs) in neurons and muscle, its greatest potency is against α7-nAchRs, which are recognized by neither short-chain α-neurotoxins nor k-neurotoxins. Given this diverse and unique pharmacology, haditoxin might have many future uses in developing molecular probes and therapeutic agents.

Structural and Functional Characterization of a Novel Homodimeric Three-finger Neurotoxin from the Venom of Ophiophagus hannah (King cobra)

Amrita Roy, Xingding Zhou, Ming Zhi Chong, Dieter D’hoedt, Chun Shin Foo, Nandhakishore Rajagopalan, Selvanayagam Nirthanan, Daniel Bertrand, J. Sivaraman and R. Manjunatha Kini

J. Biol. Chem., published online Jan. 13, 2010

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