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dc.contributor.author
Esperante, Sebastian
dc.contributor.author
Noval, María Gabriela
dc.contributor.author
Altieri, Tamara A.
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de Oliveira, Guilherme A. P.
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Silva, Jerson L.
dc.contributor.author
de Prat Gay, Gonzalo
dc.date.available
2017-06-29T20:34:14Z
dc.date.issued
2013-08-28
dc.identifier.citation
Esperante, Sebastian; Noval, María Gabriela; Altieri, Tamara A.; de Oliveira, Guilherme A. P.; Silva, Jerson L.; et al.; Fine modulation of the respiratory syncytial virus M2-1 protein quaternary structure by reversible zinc removal from its Cys(3)-His(1) motif; American Chemical Society; Biochemistry; 52; 49; 28-8-2013; 6779–6789
dc.identifier.issn
0006-2960
dc.identifier.uri
http://hdl.handle.net/11336/19212
dc.description.abstract
Human respiratory syncytial virus (hRSV) is a worldwide distributed pathogen that causes respiratory disease mostly in infants and the elderly. The M2-1 protein of hRSV functions as a transcription antiterminator and partakes in virus particle budding. It is present only in Pneumovirinae, namely, Pneumovirus (RSV) and Metapneumovirus, making it an interesting target for specific antivirals. hRSV M2-1 is a tight tetramer bearing a Cys3-His1 zinc-binding motif, present in Ebola VP30 protein and some eukaryotic proteins, whose integrity was shown to be essential for protein function but without a biochemical mechanistic basis. We showed that removal of the zinc atom causes dissociation to a monomeric apo-M2-1 species. Surprisingly, the secondary structure and stability of the apo-monomer is indistinguishable from that of the M2-1 tetramer. Dissociation reported by a highly sensitive tryptophan residue is much increased at pH 5.0 compared to pH 7.0, suggesting a histidine protonation cooperating in zinc removal. The monomeric apo form binds RNA at least as well as the tetramer, and this interaction is outcompeted by the phosphoprotein P, the RNA polymerase cofactor. The role of zinc goes beyond stabilization of local structure, finely tuning dissociation to a fully folded and binding competent monomer. Removal of zinc is equivalent to the disruption of the motif by mutation, only that the former is potentially reversible in the cellular context. Thus, this process could be triggered by a natural chelator such as glutathione or thioneins, where reversibility strongly suggests a modulatory role in the participation of M2-1 in the assembly of the polymerase complex or in virion budding.
dc.format
application/pdf
dc.language.iso
eng
dc.publisher
American Chemical Society
dc.rights
info:eu-repo/semantics/restrictedAccess
dc.rights.uri
https://creativecommons.org/licenses/by-nc-sa/2.5/ar/
dc.subject
Respiratory Syncytial Virus
dc.subject
Rna Polimerase Complex
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M2-1 Transcription Antiterminator
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Zinc Binding Motif
dc.subject.classification
Virología
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Ciencias Biológicas
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CIENCIAS NATURALES Y EXACTAS
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Biofísica
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Ciencias Biológicas
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CIENCIAS NATURALES Y EXACTAS
dc.title
Fine modulation of the respiratory syncytial virus M2-1 protein quaternary structure by reversible zinc removal from its Cys(3)-His(1) motif
dc.type
info:eu-repo/semantics/article
dc.type
info:ar-repo/semantics/artículo
dc.type
info:eu-repo/semantics/publishedVersion
dc.date.updated
2016-09-05T13:17:50Z
dc.journal.volume
52
dc.journal.number
49
dc.journal.pagination
6779–6789
dc.journal.pais
Estados Unidos
dc.journal.ciudad
Washington
dc.description.fil
Fil: Esperante, Sebastian. Consejo Nacional de Investigaciones Científicas y Técnicas. Oficina de Coordinación Administrativa Parque Centenario. Instituto de Investigaciones Bioquímicas de Buenos Aires. Fundación Instituto Leloir. Instituto de Investigaciones Bioquímicas de Buenos Aires; Argentina
dc.description.fil
Fil: Noval, María Gabriela. Consejo Nacional de Investigaciones Científicas y Técnicas. Oficina de Coordinación Administrativa Parque Centenario. Instituto de Investigaciones Bioquímicas de Buenos Aires. Fundación Instituto Leloir. Instituto de Investigaciones Bioquímicas de Buenos Aires; Argentina
dc.description.fil
Fil: Altieri, Tamara A.. Consejo Nacional de Investigaciones Científicas y Técnicas. Oficina de Coordinación Administrativa Parque Centenario. Instituto de Investigaciones Bioquímicas de Buenos Aires. Fundación Instituto Leloir. Instituto de Investigaciones Bioquímicas de Buenos Aires; Argentina
dc.description.fil
Fil: de Oliveira, Guilherme A. P.. Universidade Federal Do Rio de Janeiro. Instituto de Biologia; Brasil
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Fil: Silva, Jerson L.. Universidade Federal Do Rio de Janeiro. Instituto de Biologia; Brasil
dc.description.fil
Fil: de Prat Gay, Gonzalo. Consejo Nacional de Investigaciones Científicas y Técnicas. Oficina de Coordinación Administrativa Parque Centenario. Instituto de Investigaciones Bioquímicas de Buenos Aires. Fundación Instituto Leloir. Instituto de Investigaciones Bioquímicas de Buenos Aires; Argentina
dc.journal.title
Biochemistry
dc.relation.alternativeid
info:eu-repo/semantics/altIdentifier/doi/http://dx.doi.org/10.1021/bi401029q
dc.relation.alternativeid
info:eu-repo/semantics/altIdentifier/url/http://pubs.acs.org/doi/abs/10.1021/bi401029q


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