Fine Modulation of the Respiratory Syncytial Virus M2–1 Protein Quaternary Structure by Reversible Zinc Removal from Its Cys3-His1 Motif

• DOI: 10.1021/bi401029q
• Publication Date: 2013-08-28T16:23:38Z
• Authors: Sebastián A. Espe...; María G. Noval; Tamara A. Altieri; Guilherme A. P. d...; Jerson L. Silva; Gonzalo de Prat-Gay
• Keywords: Tetramer; Protein quaternary structure

Human respiratory syncytial virus (hRSV) is a worldwide distributed pathogen that causes disease mostly in infants and the elderly. The M2-1 protein of hRSV functions as transcription antiterminator partakes particle budding. It present only Pneumovirinae, namely, Pneumovirus (RSV) Metapneumovirus, making it an interesting target for specific antivirals. tight tetramer bearing Cys3-His1 zinc-binding motif, Ebola VP30 some eukaryotic proteins, whose integrity was shown to be essential function but without biochemical mechanistic basis. We showed removal zinc atom dissociation monomeric apo-M2-1 species. Surprisingly, secondary structure stability apo-monomer indistinguishable from tetramer. Dissociation reported by highly sensitive tryptophan residue much increased at pH 5.0 compared 7.0, suggesting histidine protonation cooperating removal. apo form binds RNA least well tetramer, this interaction outcompeted phosphoprotein P, polymerase cofactor. role goes beyond stabilization local structure, finely tuning fully folded binding competent monomer. Removal equivalent disruption motif mutation, former potentially reversible cellular context. Thus, process could triggered natural chelator such glutathione or thioneins, where reversibility strongly suggests modulatory participation assembly complex virion