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Neurotoxic phospholipase A2 from rattlesnake as a new ligand and new regulator of prokaryotic receptor GLIC (proton-gated ion channel from G. violaceus).
Ostrowski, Maciej; Porowinska, Dorota; Prochnicki, Tomasz; Prevost, Marie; Raynal, Bertrand; Baron, Bruno; Sauguet, Ludovic; Corringer, Pierre-Jean; Faure, Grazyna.
Afiliação
  • Ostrowski M; Institut Pasteur, Unité Récepteurs-Canaux, CNRS-UMR 3571, 25, rue du Dr. Roux, F-75015 Paris, France; Department of Biochemistry, Nicolaus Copernicus University, Torun, Poland.
  • Porowinska D; Institut Pasteur, Unité Récepteurs-Canaux, CNRS-UMR 3571, 25, rue du Dr. Roux, F-75015 Paris, France; Department of Biochemistry, Nicolaus Copernicus University, Torun, Poland.
  • Prochnicki T; Institut Pasteur, Unité Récepteurs-Canaux, CNRS-UMR 3571, 25, rue du Dr. Roux, F-75015 Paris, France.
  • Prevost M; Institut Pasteur, Unité Récepteurs-Canaux, CNRS-UMR 3571, 25, rue du Dr. Roux, F-75015 Paris, France.
  • Raynal B; Institu Pasteur, Plate-Forme de Biophysique des Macromolecules et de leurs Interactions, 75015 Paris, France.
  • Baron B; Institu Pasteur, Plate-Forme de Biophysique des Macromolecules et de leurs Interactions, 75015 Paris, France.
  • Sauguet L; Institut Pasteur, Unité Récepteurs-Canaux, CNRS-UMR 3571, 25, rue du Dr. Roux, F-75015 Paris, France.
  • Corringer PJ; Institut Pasteur, Unité Récepteurs-Canaux, CNRS-UMR 3571, 25, rue du Dr. Roux, F-75015 Paris, France.
  • Faure G; Institut Pasteur, Unité Récepteurs-Canaux, CNRS-UMR 3571, 25, rue du Dr. Roux, F-75015 Paris, France. Electronic address: grazyna.faure-kuzminska@pasteur.fr.
Toxicon ; 116: 63-71, 2016 Jun 15.
Article em En | MEDLINE | ID: mdl-26854368
Neurotoxic phospholipases A2 (sPLA2) from snake venoms interact with various protein targets with high specificity and potency. They regulate function of multiple receptors or channels essential to life processes including neuronal or neuromuscular chemoelectric signal transduction. These toxic sPLA2 exhibit high pharmacological potential and determination of PLA2-receptor binding sites represents challenging part in the receptor-channel biochemistry and pharmacology. To investigate the mechanism of interaction of neurotoxic PLA2 with its neuronal receptor at the molecular level, we used as a model crotoxin, a heterodimeric sPLA2 from rattlesnake venom and proton-gated ion channel GLIC, a bacterial homolog of pentameric ligand-gated ion channels. The three-dimensional structures of both partners, crotoxin and GLIC have been solved by X-ray crystallography and production of full-length pentameric GLIC (with ECD and TM domains) is well established. In the present study, for the first time, we demonstrated physical and functional interaction of full-length purified and solubilized GLIC with CB, (PLA2 subunit of crotoxin). We identified GLIC as a new protein target of CB and CB as a new ligand of GLIC, and showed that this non covalent interaction (PLA2-GLIC) involves the extracellular domain of GLIC. We also determined a novel function of CB as an inhibitor of proton-gated ion channel activity. In agreement with conformational changes observed upon formation of the complex, CB appears to be negative allosteric modulator (NAM) of GLIC. Finally, we proposed a possible stoichiometric model for CB - GLIC interaction based on analytical ultracentrifugation.
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Texto completo: 1 Coleções: 01-internacional Base de dados: MEDLINE Assunto principal: Proteínas de Bactérias / Venenos de Crotalídeos / Fosfolipases A2 / Canais Iônicos de Abertura Ativada por Ligante Limite: Animals Idioma: En Revista: Toxicon Ano de publicação: 2016 Tipo de documento: Article País de afiliação: Polônia

Texto completo: 1 Coleções: 01-internacional Base de dados: MEDLINE Assunto principal: Proteínas de Bactérias / Venenos de Crotalídeos / Fosfolipases A2 / Canais Iônicos de Abertura Ativada por Ligante Limite: Animals Idioma: En Revista: Toxicon Ano de publicação: 2016 Tipo de documento: Article País de afiliação: Polônia