The Duvernoy's gland secretory proteome of the false coral snake Rhinobothryum bovallii (Costa Rica), unveiled applying bottom-up venomics, comprises a handful of toxins belonging to only three protein families, three-finger toxin (3FTx), cysteine-rich secretory protein (CRISP), and snake venom metalloprotease (PIII-SVMP). Except for small differences in the relative abundance of the PIII-SVMPs, which may be due to individual variability, no evidence of geographic variability or ontogenetic changes was found among the venom proteomes of the juvenile and adult R. bovallii snakes sampled. Major monomeric (86.5%mol) and minor dimeric (2.8%mol) 3FTxs dominate the toxin arsenal of the Costa Rican false coral snake. The remaining 10.7% of the venom proteome comprises CRISP (8.2%) and PIII-SVMP (2.4%) molecules. In vivo lethality assays showed that R. bovallii produces venom that is non-toxic towards mammalian prey, and which exerts a different toxic effect on domestic chicken chicks and baby green iguana. Toxicovenomic analysis of R. bovallii venom in the iguana model identified two 3FTx RP-HPLC fractions that faithfully mimicked the irreversible immobilizing effect of the whole venom.

Biological significance

With more than 2200 species in family Colubridae (sensu lato), rear-fanged snakes comprise approximately two-thirds of the extant species of advanced snakes. Snakebites from venomous snakes that are of medical concern are predominantly from front-fanged snakes of families Viperidae and Elapidae. On the other hand, rear-fanged snakes have been conventionally considered non-venomous, and thus their venoms have remained a largely untapped area of venomics. However, increasing documentation of life-threadening, even fatal, envenomings from rear-fanged snakes has sparked interest in their venoms. Appying bottom-up venomics we have revealed that the Duvernoy's gland secretory proteome of R. bovallii comprises a handful of toxins belonging to only three protein families, with slow-acting three-finger toxins (3FTx) that are non-toxic towards mammalian prey and show preference towards diapsid taxa representing the dominant structural and functional proteins. Our work documents for the first time 3FTxs exerting different effect in an avian model than in a reptile model. Besides, the 3FTx fractions that faithfully mimicked the irreversible iguana-immobilizing effect of the whole venom were identified through toxicovenomic analysis of R. bovallii venom on Iguana iguana. Our work underscores the importance of using biologically-relevant animal toxicity models for investigating the biological roles of venoms in an evolutionary-ecological context.

中文翻译：

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假珊瑚蛇Rhinobothryum bovallii的Duvernoy腺分泌物的经济学（Andersson，1916），以及对突触和双足动物模型的毒力杀伤力评估。

假珊瑚蛇Rhinobothryum bovallii（哥斯达黎加）的Duvernoy腺分泌蛋白质组采用自下而上的病毒学原理揭开面纱，仅包含少数属于三个蛋白质家族的毒素，三指毒素（3FTx），富含半胱氨酸的分泌蛋白（ CRISP）和蛇毒金属蛋白酶（PIII-SVMP）。除了PIII-SVMPs相对丰度的细微差异（可能是由于个体差异）之外，在少年和成年R. bovallii的毒液蛋白质组中均未发现地理差异或个体发生变化的证据。蛇采样。主要的单体（86.5％mol）和次要的二聚体（2.8％mol）3FTxs占据了哥斯达黎加假珊瑚蛇的毒素库。毒蛋白质组的其余10.7％包括CRISP（8.2％）和PIII-SVMP（2.4％）分子。体内杀伤力测定表明，博瓦尔利氏酵母产生的毒液对哺乳动物的猎物无毒，并且对家禽和绿鬣蜥有不同的毒性作用。在鬣蜥模型中对Bovallii毒液进行的毒气动力学分析确定了两个3FTx RP-HPLC组分，它们忠实地模拟了整个毒液的不可逆固定作用。

生物学意义

Co蛇科有2200多个物种，后fang蛇约占现存蛇类的三分之二。医疗上有毒蛇的蛇咬主要来自from蛇科和E科的families蛇。另一方面，后fang蛇通常被认为是无毒的，因此它们的毒液一直是未开发的毒理学领域。但是，越来越多的有关后蛇蛇毒的生命线化甚至致命性记录的记录，引起了人们对其毒液的兴趣。应用自下而上的病毒学，我们已经揭示了杜瓦诺伊氏酵母的腺体分泌蛋白质组。包含仅属于三个蛋白质家族的少量毒素，以及对哺乳动物猎物无毒且对代表主要结构和功能蛋白的直辖分类群有偏爱的慢效三指毒素（3FTx）。我们的工作首次证明了3FTx在鸟类模型中的作用与在爬行动物模型中的作用不同。此外，通过对博瓦利蛇毒对鬣鳞蜥的毒理学分析，鉴定了忠实模仿整个蛇毒的不可逆固定化鬣蜥作用的3FTx组分。我们的工作强调了使用生物学相关的动物毒性模型来研究毒液在进化生态环境中的生物学作用的重要性。