School of Basic Medical Sciences, Wenzhou Medical University, Wenzhou, 325035, Zhejiang, China.
Key Laboratory of Animal Models and Human Disease Mechanisms of Chinese Academy of Sciences & Yunnan Province, Kunming Institute of Zoology, Kunming, 650223, Yunnan, China.
Biochem Biophys Res Commun. 2020 Jul 12;528(1):99-104. doi: 10.1016/j.bbrc.2020.05.051. Epub 2020 May 24.
A novel Kunitz-type neurotoxin peptide that inhibited voltage-gated sodium channel was purified and characterized from the skin secretions of rufous-spotted torrent frog, Amolops loloensis. It has a 240-bp cDNA encoding an 79-amino acid residue (aa) precursor protein containing 6 half-cysteines. The precursor was proven to release a 57-aa mature peptide with amino acid sequence, DRNPICNLPPKEGFCLWMMRRSFFNPSKGRCDTFGYRGCGGNKNNFETPRACKEACG. The mature was named amotoxin. Amotoxin shares sequence homology with other Kunitz-type toxins and also has three cysteine bridges. Amotoxin showed an inhibitory ability against trypsin with an inhibitory constant (Ki) of 0.087 μM. To the best of our knowledge, this is the first gene-encoded neurotoxin found in Amolops loloensis. Recombinant amotoxin showed similar functional properties as the native amotoxin. The functional properties of amotoxin may provide insights into the ecological adaptation of amphibians and deepen our understanding about the biological function spectrum of amphibian skin peptides.
一种新型的 Kunitz 型神经毒素肽，能抑制电压门控钠离子通道，从四川湍蛙（Amolops loloensis）的皮肤分泌物中被分离和鉴定。它有一个 240bp 的 cDNA 编码一个 79 个氨基酸残基（aa）的前体蛋白，包含 6 个半胱氨酸。该前体蛋白被证明可以释放一个 57 个氨基酸的成熟肽，其氨基酸序列为 DRNPICNLPPKEGFCLWMMRRSFFNPSKGRCDTFGYRGCGGNKNNFETPRACKEACG。该成熟肽被命名为amotoxin。Amotoxin 与其他 Kunitz 型毒素具有序列同源性，并且也有三个半胱氨酸桥。Amotoxin 对胰蛋白酶具有抑制能力，抑制常数（Ki）为 0.087 μM。据我们所知，这是在四川湍蛙中发现的第一个基因编码的神经毒素。重组 amotoxin 表现出与天然 amotoxin 相似的功能特性。Amotoxin 的功能特性可能为两栖动物的生态适应提供了一些见解，并加深了我们对两栖动物皮肤肽生物功能谱的理解。
