Proteogenomics-guided functional venomics resolves the toxin arsenal and activity of Deinagkistrodon acutus venom.

Autor: Avella I; Animal Venomics Lab, Fraunhofer Institute for Molecular Biology and Applied Ecology (IME), Ohlebergsweg 12, 35392 Giessen, Germany; Institute for Insect Biotechnology, Justus Liebig University Giessen, Heinrich-Buff-Ring 26-32, 35392 Giessen, Germany; LOEWE Centre for Translational Biodiversity Genomics (LOEWE-TBG), Natural Product Genomics, Senckenberganlage 25, 60325 Frankfurt am Main, Germany. Electronic address: ignazio.avella@ime.fraunhofer.de., Schulte L; Animal Venomics Lab, Fraunhofer Institute for Molecular Biology and Applied Ecology (IME), Ohlebergsweg 12, 35392 Giessen, Germany; Institute for Insect Biotechnology, Justus Liebig University Giessen, Heinrich-Buff-Ring 26-32, 35392 Giessen, Germany; LOEWE Centre for Translational Biodiversity Genomics (LOEWE-TBG), Natural Product Genomics, Senckenberganlage 25, 60325 Frankfurt am Main, Germany; Branch for Bioresources, Fraunhofer Institute for Molecular Biology and Applied Ecology (IME), Ohlebergsweg 12, 35392 Giessen, Germany., Hurka S; LOEWE Centre for Translational Biodiversity Genomics (LOEWE-TBG), Natural Product Genomics, Senckenberganlage 25, 60325 Frankfurt am Main, Germany; Branch for Bioresources, Fraunhofer Institute for Molecular Biology and Applied Ecology (IME), Ohlebergsweg 12, 35392 Giessen, Germany; BMBF Junior Research Group in Bioeconomy (BioKreativ) 'SymBioÖkonomie', Ohlebergsweg 12, 35392 Giessen, Germany., Damm M; Animal Venomics Lab, Fraunhofer Institute for Molecular Biology and Applied Ecology (IME), Ohlebergsweg 12, 35392 Giessen, Germany; Institute for Insect Biotechnology, Justus Liebig University Giessen, Heinrich-Buff-Ring 26-32, 35392 Giessen, Germany; LOEWE Centre for Translational Biodiversity Genomics (LOEWE-TBG), Natural Product Genomics, Senckenberganlage 25, 60325 Frankfurt am Main, Germany., Eichberg J; Branch for Bioresources, Fraunhofer Institute for Molecular Biology and Applied Ecology (IME), Ohlebergsweg 12, 35392 Giessen, Germany; BMBF Junior Research Group in Infection Research 'ASCRIBE', Ohlebergsweg 12, 35392 Giessen, Germany., Schiffmann S; LOEWE Centre for Translational Biodiversity Genomics (LOEWE-TBG), Natural Product Genomics, Senckenberganlage 25, 60325 Frankfurt am Main, Germany; Fraunhofer Institute for Translational Medicine and Pharmacology (ITMP), 60596 Frankfurt am Main, Germany., Henke M; LOEWE Centre for Translational Biodiversity Genomics (LOEWE-TBG), Natural Product Genomics, Senckenberganlage 25, 60325 Frankfurt am Main, Germany; Fraunhofer Institute for Translational Medicine and Pharmacology (ITMP), 60596 Frankfurt am Main, Germany., Timm T; Protein Analytics, Institute of Biochemistry, Faculty of Medicine, Justus Liebig University Giessen, Friedrichstrasse 24, 35392 Giessen, Germany., Lochnit G; Protein Analytics, Institute of Biochemistry, Faculty of Medicine, Justus Liebig University Giessen, Friedrichstrasse 24, 35392 Giessen, Germany., Hardes K; LOEWE Centre for Translational Biodiversity Genomics (LOEWE-TBG), Natural Product Genomics, Senckenberganlage 25, 60325 Frankfurt am Main, Germany; Branch for Bioresources, Fraunhofer Institute for Molecular Biology and Applied Ecology (IME), Ohlebergsweg 12, 35392 Giessen, Germany; BMBF Junior Research Group in Infection Research 'ASCRIBE', Ohlebergsweg 12, 35392 Giessen, Germany., Vilcinskas A; Institute for Insect Biotechnology, Justus Liebig University Giessen, Heinrich-Buff-Ring 26-32, 35392 Giessen, Germany; LOEWE Centre for Translational Biodiversity Genomics (LOEWE-TBG), Natural Product Genomics, Senckenberganlage 25, 60325 Frankfurt am Main, Germany; Branch for Bioresources, Fraunhofer Institute for Molecular Biology and Applied Ecology (IME), Ohlebergsweg 12, 35392 Giessen, Germany., Lüddecke T; Animal Venomics Lab, Fraunhofer Institute for Molecular Biology and Applied Ecology (IME), Ohlebergsweg 12, 35392 Giessen, Germany; LOEWE Centre for Translational Biodiversity Genomics (LOEWE-TBG), Natural Product Genomics, Senckenberganlage 25, 60325 Frankfurt am Main, Germany; Branch for Bioresources, Fraunhofer Institute for Molecular Biology and Applied Ecology (IME), Ohlebergsweg 12, 35392 Giessen, Germany. Electronic address: tim.lueddecke@ime.fraunhofer.de.
Jazyk: angličtina
Zdroj: International journal of biological macromolecules [Int J Biol Macromol] 2024 Oct; Vol. 278 (Pt 4), pp. 135041. Date of Electronic Publication: 2024 Aug 23.
DOI: 10.1016/j.ijbiomac.2024.135041
Abstrakt: Snakebite primarily impacts rural communities of Africa, Asia, and Latin America. The sharp-nosed viper (Deinagkistrodon acutus) is among the snakes of highest medical importance in Asia. Despite various studies on its venom using modern venomics techniques, a comprehensive understanding of composition and function of this species' venom remains lacking. We combined proteogenomics with extensive bioactivity profiling to present the first genome-level catalogue of D. acutus venom proteins and their exochemistry. Our analysis identified an unusually simple venom containing 45 components from 20 distinct protein families. Relative toxin abundances indicate that C-type lectin and C-type lectin-related protein (CTL), snake venom metalloproteinase (svMP), snake venom serine protease (svSP), and phospholipase A 2 (PLA 2 ) constitute 90 % of the venom. Bioassays targeting key aspects of viperid envenomation showed considerable concentration-dependent cytotoxicity, particularly in kidney and lung cells, and potent protease and PLA 2 activity. Factor Xa and thrombin activities were minor, and no plasmin activity was observed. Effects on haemolysis, intracellular calcium (Ca 2+ ) release, and nitric oxide (NO) synthesis were negligible. Our analysis provides the first holistic genome-based overview of the toxin arsenal of D. acutus, predicting the molecular and functional basis of its life-threatening effects, and opens novel avenues for treating envenomation by this highly dangerous snake.
Competing Interests: Declaration of competing interest The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper.
(Copyright © 2024 The Authors. Published by Elsevier B.V. All rights reserved.)
Databáze: MEDLINE
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