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Atroxlysin-III, A Metalloproteinase from the Venom of the Peruvian Pit Viper Snake Bothrops atrox (Jergón) Induces Glycoprotein VI Shedding and Impairs Platelet Function
Atroxlysin-III (Atr-III) was purified from the venom of Bothrops atrox. This 56-kDa protein bears N-linked glycoconjugates and is a P-III hemorrhagic metalloproteinase. Its cDNA-deduced amino acid sequence reveals a multidomain structure including a proprotein, a metalloproteinase, a disintegrin-lik...
Autores principales: | , , , , , , , , |
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Formato: | Online Artículo Texto |
Lenguaje: | English |
Publicado: |
MDPI
2019
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Materias: | |
Acceso en línea: | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC6803841/ https://www.ncbi.nlm.nih.gov/pubmed/31561469 http://dx.doi.org/10.3390/molecules24193489 |
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author | Oliveira, Luciana S. Estevão-Costa, Maria Inácia Alvarenga, Valéria G. Vivas-Ruiz, Dan E. Yarleque, Armando Lima, Augusto Martins Cavaco, Ana Eble, Johannes A. Sanchez, Eladio F. |
author_facet | Oliveira, Luciana S. Estevão-Costa, Maria Inácia Alvarenga, Valéria G. Vivas-Ruiz, Dan E. Yarleque, Armando Lima, Augusto Martins Cavaco, Ana Eble, Johannes A. Sanchez, Eladio F. |
author_sort | Oliveira, Luciana S. |
collection | PubMed |
description | Atroxlysin-III (Atr-III) was purified from the venom of Bothrops atrox. This 56-kDa protein bears N-linked glycoconjugates and is a P-III hemorrhagic metalloproteinase. Its cDNA-deduced amino acid sequence reveals a multidomain structure including a proprotein, a metalloproteinase, a disintegrin-like and a cysteine-rich domain. Its identity with bothropasin and jararhagin from Bothrops jararaca is 97% and 95%, respectively. Its enzymatic activity is metal ion-dependent. The divalent cations, Mg(2+) and Ca(2+), enhance its activity, whereas excess Zn(2+) inhibits it. Chemical modification of the Zn(2+)-complexing histidine residues within the active site by using diethylpyrocarbonate (DEPC) inactivates it. Atr-III degrades plasma fibronectin, type I-collagen, and mainly the α-chains of fibrinogen and fibrin. The von Willebrand factor (vWF) A1-domain, which harbors the binding site for GPIb, is not hydrolyzed. Platelets interact with collagen via receptors for collagen, glycoprotein VI (GPVI), and α2β1 integrin. Neither the α2β1 integrin nor its collagen-binding A-domain is fragmented by Atr-III. In contrast, Atr-III cleaves glycoprotein VI (GPVI) into a soluble ~55-kDa fragment (sGPVI). Thereby, it inhibits aggregation of platelets which had been stimulated by convulxin, a GPVI agonist. Selectively, Atr-III targets GPVI antagonistically and thus contributes to the antithrombotic effect of envenomation by Bothrops atrox. |
format | Online Article Text |
id | pubmed-6803841 |
institution | National Center for Biotechnology Information |
language | English |
publishDate | 2019 |
publisher | MDPI |
record_format | MEDLINE/PubMed |
spelling | pubmed-68038412019-11-18 Atroxlysin-III, A Metalloproteinase from the Venom of the Peruvian Pit Viper Snake Bothrops atrox (Jergón) Induces Glycoprotein VI Shedding and Impairs Platelet Function Oliveira, Luciana S. Estevão-Costa, Maria Inácia Alvarenga, Valéria G. Vivas-Ruiz, Dan E. Yarleque, Armando Lima, Augusto Martins Cavaco, Ana Eble, Johannes A. Sanchez, Eladio F. Molecules Article Atroxlysin-III (Atr-III) was purified from the venom of Bothrops atrox. This 56-kDa protein bears N-linked glycoconjugates and is a P-III hemorrhagic metalloproteinase. Its cDNA-deduced amino acid sequence reveals a multidomain structure including a proprotein, a metalloproteinase, a disintegrin-like and a cysteine-rich domain. Its identity with bothropasin and jararhagin from Bothrops jararaca is 97% and 95%, respectively. Its enzymatic activity is metal ion-dependent. The divalent cations, Mg(2+) and Ca(2+), enhance its activity, whereas excess Zn(2+) inhibits it. Chemical modification of the Zn(2+)-complexing histidine residues within the active site by using diethylpyrocarbonate (DEPC) inactivates it. Atr-III degrades plasma fibronectin, type I-collagen, and mainly the α-chains of fibrinogen and fibrin. The von Willebrand factor (vWF) A1-domain, which harbors the binding site for GPIb, is not hydrolyzed. Platelets interact with collagen via receptors for collagen, glycoprotein VI (GPVI), and α2β1 integrin. Neither the α2β1 integrin nor its collagen-binding A-domain is fragmented by Atr-III. In contrast, Atr-III cleaves glycoprotein VI (GPVI) into a soluble ~55-kDa fragment (sGPVI). Thereby, it inhibits aggregation of platelets which had been stimulated by convulxin, a GPVI agonist. Selectively, Atr-III targets GPVI antagonistically and thus contributes to the antithrombotic effect of envenomation by Bothrops atrox. MDPI 2019-09-26 /pmc/articles/PMC6803841/ /pubmed/31561469 http://dx.doi.org/10.3390/molecules24193489 Text en © 2019 by the authors. Licensee MDPI, Basel, Switzerland. This article is an open access article distributed under the terms and conditions of the Creative Commons Attribution (CC BY) license (http://creativecommons.org/licenses/by/4.0/). |
spellingShingle | Article Oliveira, Luciana S. Estevão-Costa, Maria Inácia Alvarenga, Valéria G. Vivas-Ruiz, Dan E. Yarleque, Armando Lima, Augusto Martins Cavaco, Ana Eble, Johannes A. Sanchez, Eladio F. Atroxlysin-III, A Metalloproteinase from the Venom of the Peruvian Pit Viper Snake Bothrops atrox (Jergón) Induces Glycoprotein VI Shedding and Impairs Platelet Function |
title | Atroxlysin-III, A Metalloproteinase from the Venom of the Peruvian Pit Viper Snake Bothrops atrox (Jergón) Induces Glycoprotein VI Shedding and Impairs Platelet Function |
title_full | Atroxlysin-III, A Metalloproteinase from the Venom of the Peruvian Pit Viper Snake Bothrops atrox (Jergón) Induces Glycoprotein VI Shedding and Impairs Platelet Function |
title_fullStr | Atroxlysin-III, A Metalloproteinase from the Venom of the Peruvian Pit Viper Snake Bothrops atrox (Jergón) Induces Glycoprotein VI Shedding and Impairs Platelet Function |
title_full_unstemmed | Atroxlysin-III, A Metalloproteinase from the Venom of the Peruvian Pit Viper Snake Bothrops atrox (Jergón) Induces Glycoprotein VI Shedding and Impairs Platelet Function |
title_short | Atroxlysin-III, A Metalloproteinase from the Venom of the Peruvian Pit Viper Snake Bothrops atrox (Jergón) Induces Glycoprotein VI Shedding and Impairs Platelet Function |
title_sort | atroxlysin-iii, a metalloproteinase from the venom of the peruvian pit viper snake bothrops atrox (jergón) induces glycoprotein vi shedding and impairs platelet function |
topic | Article |
url | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC6803841/ https://www.ncbi.nlm.nih.gov/pubmed/31561469 http://dx.doi.org/10.3390/molecules24193489 |
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