Coralsnake Venomics: Analyses of Venom Gland Transcriptomes and Proteomes of Six Brazilian Taxa.
Coralsnake Venomics: Analyses of Venom Gland Transcriptomes and Proteomes of Six Brazilian Taxa.
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DOI：
10.3390/toxins9060187
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发表时间：
2017-06-08
期刊：
影响因子：
4.2
通讯作者：
Mikheyev AS
中科院分区：
文献类型：
--
作者：
Aird SD;da Silva NJ;Qiu L;Villar-Briones A;Saddi VA;Pires de Campos Telles M;Grau ML;Mikheyev AS
本文对六种小尾蛇的毒腺转录组和蛋白质组进行了研究。corpus，M. lemniscatus carvalhoi，M. lemniscatus lemniscatus，M. paraensis，M. spixii spixii和M. surinamensis）进行了研究，提供了迄今为止关于Micrurus毒液组成的最全面的定量数据，并且使先前可用的Micrurus毒液蛋白质序列的数量增加了两倍多。六种毒液组差别很大。所有这些都由2-6种毒素类占主导地位，占毒素转录本的91-99%。分枝S. spixii毒液组在组成上是最简单的。其中，三指毒素（3FTxs）和磷脂酶A2（PLA 2）占毒素转录本的99%以上，其中仅包括水平≥ 0.1%的四个额外的毒素家族。[医]小蓟属lemniscatus毒液是最复杂的，至少有17个毒素家族。然而，在每个毒液组中，存在3FTX和PLA 2的多个结构亚类。这些药物在药理学上也几乎肯定不同。所有毒液还含有磷脂酶B和血管内皮生长因子。除M外，其它所有毒液中均含有微量成分（0.1-2.0%）。S. spixii。其他毒素家族在所有六种毒液中都以痕量水平存在（<0.005%）。微量和微量毒液成分在每种毒液中不同。许多新的毒素化学包括具有先前未知的8-和10-半胱氨酸排列的3FTx，从而产生新的3D结构和靶特异性。9-半胱氨酸毒素提高了共价的、同二聚体3FTx或具有未知药理学的异二聚体毒素的可能性。可能的毒蕈碱序列可能是爬行动物特异性同源物，通过血管mAChRs促进低血压。第一个完整的序列是负责从大鼠脑突触体中释放谷氨酸的3FTxs puronectin。Micrurus C型凝集素样蛋白可能具有6-9个半胱氨酸残基，并且可能是单体，或药理学未知的同源或异源二聚体。新的KSPIs，比以前看到的长3倍，似乎是通过基因复制和融合在三个物种中出现的。四个物种具有与伤害性毒素（MitTx）α亚基同源的转录本，但所有六个物种都具有与β亚基的同源物。报道了第一个无神经毒性、无催化活性的磷脂酶A2。可能都是肌坏死。系统发育分析表明，这六个类群在1500万至3500万年前分化，它们在近5500万年前与旧大陆elapines的最后一个共同祖先分离。由于其早期的多样化，许多神秘的micrurine类群是预期的。
Venom gland transcriptomes and proteomes of six Micrurus taxa (M. corallinus, M. lemniscatus carvalhoi, M. lemniscatus lemniscatus, M. paraensis, M. spixii spixii, and M. surinamensis) were investigated, providing the most comprehensive, quantitative data on Micrurus venom composition to date, and more than tripling the number of Micrurus venom protein sequences previously available. The six venomes differ dramatically. All are dominated by 2–6 toxin classes that account for 91–99% of the toxin transcripts. The M. s. spixii venome is compositionally the simplest. In it, three-finger toxins (3FTxs) and phospholipases A2 (PLA2s) comprise >99% of the toxin transcripts, which include only four additional toxin families at levels ≥0.1%. Micrurus l. lemniscatus venom is the most complex, with at least 17 toxin families. However, in each venome, multiple structural subclasses of 3FTXs and PLA2s are present. These almost certainly differ in pharmacology as well. All venoms also contain phospholipase B and vascular endothelial growth factors. Minor components (0.1–2.0%) are found in all venoms except that of M. s. spixii. Other toxin families are present in all six venoms at trace levels (<0.005%). Minor and trace venom components differ in each venom. Numerous novel toxin chemistries include 3FTxs with previously unknown 8- and 10-cysteine arrangements, resulting in new 3D structures and target specificities. 9-cysteine toxins raise the possibility of covalent, homodimeric 3FTxs or heterodimeric toxins with unknown pharmacologies. Probable muscarinic sequences may be reptile-specific homologs that promote hypotension via vascular mAChRs. The first complete sequences are presented for 3FTxs putatively responsible for liberating glutamate from rat brain synaptosomes. Micrurus C-type lectin-like proteins may have 6–9 cysteine residues and may be monomers, or homo- or heterodimers of unknown pharmacology. Novel KSPIs, 3× longer than any seen previously, appear to have arisen in three species by gene duplication and fusion. Four species have transcripts homologous to the nociceptive toxin, (MitTx) α-subunit, but all six species had homologs to the β-subunit. The first non-neurotoxic, non-catalytic elapid phospholipase A2s are reported. All are probably myonecrotic. Phylogenetic analysis indicates that the six taxa diverged 15–35 million years ago and that they split from their last common ancestor with Old World elapines nearly 55 million years ago. Given their early diversification, many cryptic micrurine taxa are anticipated.