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下一代蛇毒组学:通过毒液蛋白质组去复合物解析实现蛋白质基因座分辨率。

Next-generation snake venomics: protein-locus resolution through venom proteome decomplexation.

机构信息

Instituto de Biomedicina de Valencia, Consejo Superior de Investigaciones Científicas, Jaime Roig 11, 46010 Valencia, Spain +34 963 391 778 +34 963 690 800

出版信息

Expert Rev Proteomics. 2014 Jun;11(3):315-29. doi: 10.1586/14789450.2014.900447. Epub 2014 Mar 29.

DOI:10.1586/14789450.2014.900447
PMID:24678852
Abstract

Venom research has been continuously enhanced by technological advances. High-throughput technologies are changing the classical paradigm of hypothesis-driven research to technology-driven approaches. However, the thesis advocated in this paper is that full proteome coverage at locus-specific resolution requires integrating the best of both worlds into a protocol that includes decomplexation of the venom proteome prior to liquid chromatography-tandem mass spectrometry matching against a species-specific transcriptome. This approach offers the possibility of proof-checking the species-specific contig database using proteomics data. Immunoaffinity chromatography constitutes the basis of an antivenomics workflow designed to quantify the extent of cross-reactivity of antivenoms against homologous and heterologous venom toxins. In the author's view, snake venomics and antivenomics form part of a biology-driven conceptual framework to unveil the genesis and natural history of venoms, and their within- and between-species toxicological and immunological divergences and similarities. Understanding evolutionary trends across venoms represents the Rosetta Stone for generating broad-ranging polyspecific antivenoms.

摘要

毒液研究一直受到技术进步的推动。高通量技术正在改变基于假设的经典研究范式,转而采用基于技术的方法。然而,本文所主张的观点是,要实现特定位置的全蛋白质组覆盖,需要将这两种方法的优势整合到一个方案中,即在进行液相色谱-串联质谱匹配与物种特异性转录组之前,先对毒液蛋白质组进行去复合物化处理。这种方法提供了使用蛋白质组学数据来验证物种特异性连续体数据库的可能性。免疫亲和层析构成了抗蛇毒组学工作流程的基础,该工作流程旨在定量抗蛇毒血清对同源和异源毒液毒素的交叉反应程度。作者认为,蛇毒组学和抗蛇毒组学是一个生物学驱动的概念框架的一部分,旨在揭示毒液的起源和自然历史,以及它们在物种内和物种间的毒理学和免疫学差异和相似性。了解毒液的进化趋势是生成广泛的多特异性抗蛇毒血清的关键。

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