Mostrar el registro sencillo del ítem

dc.contributor.authorDao, Khanh K.
dc.contributor.authorPey Rodríguez, Ángel Luis 
dc.contributor.authorGjerde, Anja Underhaug
dc.contributor.authorTeigen, Knut
dc.contributor.authorByeon, In-Ja L.
dc.contributor.authorDøskeland, Stein O.
dc.contributor.authorGronenborn, Angela M.
dc.contributor.authorMartínez, Aurora
dc.date.accessioned2014-03-26T12:37:13Z
dc.date.available2014-03-26T12:37:13Z
dc.date.issued2011
dc.identifier.citationDao, K.K.; et al. The Regulatory Subunit of PKA-I Remains Partially Structured and Undergoes β-Aggregation upon Thermal Denaturation. Plos One, 6(3): e17602 (2011). [http://hdl.handle.net/10481/31128]es_ES
dc.identifier.issn1932-6203
dc.identifier.otherdoi: 10.1371/journal.pone.0017602
dc.identifier.urihttp://hdl.handle.net/10481/31128
dc.description.abstract[Background] The regulatory subunit (R) of cAMP-dependent protein kinase (PKA) is a modular flexible protein that responds with large conformational changes to the binding of the effector cAMP. Considering its highly dynamic nature, the protein is rather stable. We studied the thermal denaturation of full-length RIα and a truncated RIα(92-381) that contains the tandem cyclic nucleotide binding (CNB) domains A and B. [Methodology/Principal Findings] As revealed by circular dichroism (CD) and differential scanning calorimetry, both RIα proteins contain significant residual structure in the heat-denatured state. As evidenced by CD, the predominantly α-helical spectrum at 25°C with double negative peaks at 209 and 222 nm changes to a spectrum with a single negative peak at 212–216 nm, characteristic of β-structure. A similar α→β transition occurs at higher temperature in the presence of cAMP. Thioflavin T fluorescence and atomic force microscopy studies support the notion that the structural transition is associated with cross-β-intermolecular aggregation and formation of non-fibrillar oligomers. [Conclusions/Significance] Thermal denaturation of RIα leads to partial loss of native packing with exposure of aggregation-prone motifs, such as the B' helices in the phosphate-binding cassettes of both CNB domains. The topology of the β-sandwiches in these domains favors inter-molecular β-aggregation, which is suppressed in the ligand-bound states of RIα under physiological conditions. Moreover, our results reveal that the CNB domains persist as structural cores through heat-denaturation.es_ES
dc.description.sponsorshipThis research was financed in part with grants from The Research Council of Norway and the Norwegian Cancer Society (to AM and SOD). ALP is supported by a Ramon y Cajal research contract from the Spanish Ministry of Sciences and Innovation (MICINN).es_ES
dc.language.isoenges_ES
dc.publisherPublic Library of Science (PLOS)es_ES
dc.rightsCreative Commons Attribution-NonCommercial-NoDerivs 3.0 Licensees_ES
dc.rights.urihttp://creativecommons.org/licenses/by-nc-nd/3.0/es_ES
dc.subjectAtomic force microscopyes_ES
dc.subjectBiochemical simulationses_ES
dc.subjectCricular dichroism spectroscopyes_ES
dc.subjectCrystal structurees_ES
dc.subjectFluorescence es_ES
dc.subjectFluorescence microscopyes_ES
dc.subjectProtein structurees_ES
dc.subjectThermal stabilityes_ES
dc.titleThe Regulatory Subunit of PKA-I Remains Partially Structured and Undergoes β-Aggregation upon Thermal Denaturationes_ES
dc.typeinfo:eu-repo/semantics/articlees_ES
dc.rights.accessRightsinfo:eu-repo/semantics/openAccesses_ES


Ficheros en el ítem

[PDF]

Este ítem aparece en la(s) siguiente(s) colección(ones)

Mostrar el registro sencillo del ítem

Creative Commons Attribution-NonCommercial-NoDerivs 3.0 License
Excepto si se señala otra cosa, la licencia del ítem se describe como Creative Commons Attribution-NonCommercial-NoDerivs 3.0 License