8bo0
From Proteopedia
Solution structure of Lqq4 toxin from Leiurus quinquestriatus quinquestriatus
Structural highlights
FunctionSCX4_LEIQU Alpha toxins bind voltage-independently at site-3 of sodium channels (Nav) and inhibit the inactivation of the activated channels, thereby blocking neuronal transmission. Both native and recombinant (non-amidated) toxins inhibit inactivation of Nav1.2/SCN2A (EC(50)=31.2-36.6 nM), Nav1.6/SCN8A (EC(50)=6.9-8.9 nM), and Nav1.7/SCN9A (EC(50)=182.0-260.1 nM).[1] Publication Abstract from PubMedScorpion alpha-toxins (alpha-NaTx) inhibiting the inactivation of voltage-gated sodium channels (Na(v) ) are a well-studied family of small proteins. We previously showed that the structure of alpha-NaTx specificity module responsible for selective Na(v) binding is governed by an interplay between the nest and niche protein motifs. Here, we report the solution structure of the toxin Lqq4 from the venom of the scorpion Leiurus quinquestriatus. Unexpectedly, we find that this toxin presents an ensemble of long-lived structurally distinct states. We unequivocally assign these states to the alternative configurations (cis-trans isomers) of two peptide bonds: V56-P57 and C17-G18; neither of the cis isomers has been described in alpha-NaTx so far. We argue that the native conformational space of alpha-NaTx is wider than assumed previously. A scorpion toxin affecting sodium channels shows double cis-trans isomerism.,Mineev KS, Chernykh MA, Motov VV, Prudnikova DA, Pavlenko DM, Kuzmenkov AI, Peigneur S, Tytgat J, Vassilevski AA FEBS Lett. 2023 Sep;597(18):2358-2368. doi: 10.1002/1873-3468.14705. Epub 2023 , Aug 7. PMID:37501371[2] From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine. References
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