1. RODNA
  2. FCEN
  3. FCEN - Facultad de Ciencias Exactas y Naturales. UBA
Registro completo de metadatos
Campo DC Valor Lengua/Idioma
dc.provenanceFacultad de Ciencias Exactas y Naturales de la UBA-
dc.contributor<div class="autor_fcen" id="8181">Smal, C.</div>-
dc.contributor<div class="autor_fcen" id="184">Alonso, L.G.</div>-
dc.contributor<div class="autor_fcen" id="9168">Wetzler, D.E.</div>-
dc.contributor<div class="autor_fcen" id="4208">Heer, A.</div>-
dc.contributor<div class="autor_fcen" id="2390">de Prat Gay, G.</div>-
dc.creator<div class="autor_fcen" id="8181">Smal, C.</div>-
dc.creator<div class="autor_fcen" id="184">Alonso, L.G.</div>-
dc.creator<div class="autor_fcen" id="9168">Wetzler, D.E.</div>-
dc.creator<div class="autor_fcen" id="4208">Heer, A.</div>-
dc.creator<div class="autor_fcen" id="2390">de Prat Gay, G.</div>-
dc.date.accessioned2018-05-04T22:04:13Z-
dc.date.accessioned2018-05-28T15:49:18Z-
dc.date.available2018-05-04T22:04:13Z-
dc.date.available2018-05-28T15:49:18Z-
dc.date.issued2012-
dc.identifier.urihttp://10.0.0.11:8080/jspui/handle/bnmm/68628-
dc.descriptionBackground: Self-assembly is a common theme in proteins of unrelated sequences or functions. The human papillomavirus E7 oncoprotein is an extended dimer with an intrinsically disordered domain, that can form large spherical oligomers. These are the major species in the cytosol of HPV transformed and cancerous cells. E7 binds to a large number of targets, some of which lead to cell transformation. Thus, the assembly process not only is of biological relevance, but represents a model system to investigate a widely distributed mechanism. Methodology/Principal Findings: Using various techniques, we monitored changes in secondary, tertiary and quaternary structure in a time course manner. By applying a robust kinetic model developed by Zlotnik, we determined the slow formation of a monomeric "Z-nucleus" after zinc removal, followed by an elongation phase consisting of sequential second-order events whereby one monomer is added at a time. This elongation process takes place at a strikingly slow overall average rate of one monomer added every 28 seconds at 20 μM protein concentration, strongly suggesting either a rearrangement of the growing complex after binding of each monomer or the existence of a "conformation editing" mechanism through which the monomer binds and releases until the appropriate conformation is adopted. The oligomerization determinant lies within its small 5 kDa C-terminal globular domain and, remarkably, the E7 N-terminal intrinsically disordered domain stabilizes the oligomer, preventing an insoluble amyloid route. Conclusion: We described a controlled ordered mechanism with features in common with soluble amyloid precursors, chaperones, and other spherical oligomers, thus sharing determining factors for symmetry, size and shape. In addition, such a controlled and discrete polymerization reaction provides a valuable tool for nanotechnological applications. Finally, its increased immunogenicity related to its supramolecular structure is the basis for the development of a promising therapeutic vaccine candidate for treating HPV cancerous lesions. © 2012 Smal et al.-
dc.descriptionFil:Smal, C. Universidad de Buenos Aires. Facultad de Ciencias Exactas y Naturales; Argentina.-
dc.descriptionFil:Alonso, L.G. Universidad de Buenos Aires. Facultad de Ciencias Exactas y Naturales; Argentina.-
dc.descriptionFil:Wetzler, D.E. Universidad de Buenos Aires. Facultad de Ciencias Exactas y Naturales; Argentina.-
dc.descriptionFil:Heer, A. Universidad de Buenos Aires. Facultad de Ciencias Exactas y Naturales; Argentina.-
dc.descriptionFil:de Prat Gay, G. Universidad de Buenos Aires. Facultad de Ciencias Exactas y Naturales; Argentina.-
dc.formatapplication/pdf-
dc.languageeng-
dc.rightsinfo:eu-repo/semantics/openAccess-
dc.rightshttp://creativecommons.org/licenses/by/2.5/ar-
dc.sourcePLoS ONE 2012;7(5)-
dc.source.urihttp://digital.bl.fcen.uba.ar/Download/paper/paper_19326203_v7_n5_p_Smal.pdf-
dc.subjectamyloid precursor protein-
dc.subjectamyloid protein-
dc.subjectchaperone-
dc.subjectoligomer-
dc.subjectprotein E7-
dc.subjectzinc-
dc.subjectoncogene protein E7, Human papillomavirus type 16-
dc.subjectzinc-
dc.subjectamino terminal sequence-
dc.subjectarticle-
dc.subjectcarboxy terminal sequence-
dc.subjectcircular dichroism-
dc.subjectconcentration (parameters)-
dc.subjectdrug research-
dc.subjectimmunogenicity-
dc.subjectkinetics-
dc.subjectnanotechnology-
dc.subjectoligomerization-
dc.subjectprotein assembly-
dc.subjectprotein binding-
dc.subjectprotein conformation-
dc.subjectprotein domain-
dc.subjectprotein polymerization-
dc.subjectprotein quaternary structure-
dc.subjectprotein secondary structure-
dc.subjectprotein stability-
dc.subjectprotein tertiary structure-
dc.subjectWart virus-
dc.subjectchemistry-
dc.subjectgenetics-
dc.subjecthuman-
dc.subjectHuman papillomavirus type 16-
dc.subjectmetabolism-
dc.subjectprotein multimerization-
dc.subjectHuman papillomavirus-
dc.subjectHuman papillomavirus 16-
dc.subjectHumans-
dc.subjectPapillomavirus E7 Proteins-
dc.subjectProtein Multimerization-
dc.subjectProtein Stability-
dc.subjectProtein Structure, Quaternary-
dc.subjectProtein Structure, Tertiary-
dc.subjectZinc-
dc.titleOrdered self-assembly mechanism of a spherical oncoprotein oligomer triggered by zinc removal and stabilized by an intrinsically disordered domain-
dc.typeinfo:eu-repo/semantics/article-
dc.typeinfo:ar-repo/semantics/artículo-
dc.typeinfo:eu-repo/semantics/publishedVersion-
Aparece en las colecciones: FCEN - Facultad de Ciencias Exactas y Naturales. UBA

Ficheros en este ítem:
No hay ficheros asociados a este ítem.
Mostrar el registro sencillo del ítem