近日,,中國科學(xué)院昆明動(dòng)物研究所研究員賴仞、中國科學(xué)院上海藥物研究所研究員林東海、湖南師范大學(xué)教授梁宋平等率領(lǐng)的研究團(tuán)隊(duì),,通過合作,,從華西雨蛙的皮膚分泌液中發(fā)現(xiàn)了基因編碼的神經(jīng)毒,被命名為anntoxin,。該毒素含有60個(gè)氨基酸殘基,、擁有2個(gè)分子內(nèi)二硫鍵、通過阻斷河豚毒素敏感的鈉通道發(fā)揮神經(jīng)毒活性,。該毒素主要分布于華西雨蛙皮膚中,,其含量高達(dá)25微克/克皮膚濕組織。它對昆蟲,、爬行類,、鳥類和哺乳類動(dòng)物具有強(qiáng)的致死毒性。Anntoxin與眼鏡蛇毒來源的神經(jīng)毒有顯著的結(jié)構(gòu)同源性,,也表現(xiàn)部分生物活性的相似性,。這些結(jié)構(gòu)和功能相似性暗示了動(dòng)物毒素的一種可能的進(jìn)化聯(lián)系。以前也有關(guān)于兩棲動(dòng)物南美箭毒蛙的生物堿毒素的報(bào)道,,但其不是由基因編碼的,,而是來源于其食物(如昆蟲),是不可遺傳的,,而目前發(fā)現(xiàn)的兩棲動(dòng)物神經(jīng)毒素為基因編碼產(chǎn)物,。
在魚類、爬行類、哺乳類動(dòng)物以及無脊椎動(dòng)物中早已發(fā)現(xiàn)了大量的基因編碼的神經(jīng)毒,,卻一直沒有從兩棲動(dòng)物中發(fā)現(xiàn)基因編碼的神經(jīng)毒,。
該研究成果已正式發(fā)表于國際著名學(xué)術(shù)刊物J Biol Chem. 2009,284(33):22079-86上,,題目為The First Gene-encoded Amphibian Neurotoxin,,并被美國生物化學(xué)與分子生物學(xué)聯(lián)合會作為亮點(diǎn)工作重點(diǎn)報(bào)道。(生物谷Bioon.com)
生物谷推薦原始出處:
J. Biol. Chem., Vol. 284, Issue 33, 22079-22086, August 14, 2009
The First Gene-encoded Amphibian Neurotoxin*
Dewen You1, Jing Hong?1, Mingqiang Rong||1, Haining Yu**, Songping Liang||, Yufang Ma, Hailong Yang, Jing Wu, Donghai Lin?2, and Ren Lai3
From the From the Biotoxin Units of Key Laboratory of Animal Models and Human Disease Mechanisms, Kunming Institute of Zoology, Chinese Academy of Sciences, Kunming 650223, Yunnan, , the ?Shanghai Institute of Materia Medica, Chinese Academy of Sciences, Shanghai 201203, , the ||The Key Laboratory of Protein Chemistry and Developmental Biology of Ministry of Education, College of Life Sciences, Hunan Normal University, Changsha 410081, , the **College of Life Sciences, Hebei Normal University, Shijiazhuang 050016, Hebei, and , the Graduate School of the Chinese Academy of Sciences, Beijing 100009, China
Many gene-encoded neurotoxins with various functions have been discovered in fish, reptiles, and mammals. A novel 60-residue neurotoxin peptide (anntoxin) that inhibited tetrodotoxin-sensitive (TTX-S) voltage-gated sodium channel (VGSC) was purified and characterized from the skin secretions of the tree frog Hyla annectans (Jerdon). This is the first gene-encoded neurotoxin found in amphibians. The IC50 of anntoxin for the TTX-S channel was about 3.4 μM. Anntoxin shares sequence homology with Kunitz-type toxins but contains only two of three highly conserved cysteine bridges, which are typically found in these small, basic neurotoxin modules, i.e. snake dendrotoxins. Anntoxin showed an inhibitory ability against trypsin with an inhibitory constant (Ki) of 0.025 μM. Anntoxin was distributed in skin, brain, stomach, and liver with a concentration of 25, 7, 3, and 2 μg/g wet tissue, respectively. H. annectans lives on trees or other plants for its entire life cycle, and its skin contains the largest amount of anntoxin, which possibly helps defend against various aggressors or predators. A low dose of anntoxin was found to induce lethal toxicity for several potential predators, including the insect, snake, bird, and mouse. The tissue distribution and functional properties of the current toxin may provide insights into the ecological adaptation of tree-living amphibians.