Mineev Konstantin S, Chernykh Mikhail A, Motov Vladislav V, Prudnikova Daria A, Pavlenko Daniil M, Kuzmenkov Alexey I, Peigneur Steve, Tytgat Jan, Vassilevski Alexander A
Shemyakin-Ovchinnikov Institute of Bioorganic Chemistry, Russian Academy of Sciences, Moscow, Russia.
Moscow Institute of Physics and Technology, Dolgoprudny, Russia.
FEBS Lett. 2023 Sep;597(18):2358-2368. doi: 10.1002/1873-3468.14705. Epub 2023 Aug 7.
Scorpion α-toxins (α-NaTx) inhibiting the inactivation of voltage-gated sodium channels (Na ) are a well-studied family of small proteins. We previously showed that the structure of α-NaTx specificity module responsible for selective Na 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 α-NaTx so far. We argue that the native conformational space of α-NaTx is wider than assumed previously.
抑制电压门控钠通道（Na⁺）失活的蝎毒α-毒素（α-NaTx）是一个经过充分研究的小蛋白家族。我们之前表明，负责选择性结合Na⁺的α-NaTx特异性模块的结构受巢状和小生境蛋白基序之间相互作用的支配。在此，我们报道了来自以色列金蝎毒液的毒素Lqq4的溶液结构。出乎意料的是，我们发现这种毒素呈现出一组寿命较长、结构不同的状态。我们明确地将这些状态归因于两个肽键：V56 - P57和C17 - G18的交替构象（顺反异构体）；到目前为止，α-NaTx中尚未描述过顺式异构体。我们认为α-NaTx的天然构象空间比之前假设的更宽。
