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dc.date.accessioned | 2019-12-20T18:17:33Z | |
dc.date.available | 2019-12-20T18:17:33Z | |
dc.date.issued | 2012 | |
dc.identifier.uri | http://sedici.unlp.edu.ar/handle/10915/87841 | |
dc.description.abstract | β2-syntrophin, a dystrophin-associated protein, plays a pivotal role in insulin secretion by pancreatic β-cells. It contains a PDZ domain (β2S-PDZ) that, in complex with protein-tyrosine phosphatase ICA512, anchors the dense insulin granules to actin filaments. The phosphorylation state of β2-syntrophin allosterically regulates the affinity of β2S-PDZ for ICA512, and the disruption of the complex triggers the mobilization of the insulin granule stores. Here, we investigate the thermal unfolding of β2S-PDZ at different pH and urea concentrations. Our results indicate that, unlike other PDZ domains, β2S-PDZ is marginally stable. Thermal denaturation experiments show broad transitions and cold denaturation, and a two-state model fit reveals a significant unfolded fraction under physiological conditions. Furthermore, Tm and Tmax denaturant-dependent shifts and noncoincidence of melting curves monitored at different wavelengths suggest that two-state and three-state models fail to explain the equilibrium data properly and are in better agreement with a downhill scenario. Its higher stability at pH > 9 and the results of molecular dynamics simulations indicate that this behavior of β2S-PDZ might be related to its charge distribution. All together, our results suggest a link between the conformational plasticity of the native ensemble of this PDZ domain and the regulation of insulin secretion. | en |
dc.format.extent | 2835-2844 | es |
dc.language | en | es |
dc.subject | β2-syntrophin | es |
dc.subject | PDZ domain | es |
dc.title | Equilibrium unfolding of the PDZ domain of β2-syntrophin | en |
dc.type | Articulo | es |
sedici.identifier.other | doi:10.1016/j.bpj.2012.05.021 | es |
sedici.identifier.other | eid:2-s2.0-84862639460 | es |
sedici.identifier.issn | 0006-3495 | es |
sedici.creator.person | Torchio, Gabriela María | es |
sedici.creator.person | Ermácora, Mario Roberto | es |
sedici.creator.person | Sica, Mauricio Pablo | es |
sedici.subject.materias | Ciencias Exactas | es |
sedici.description.fulltext | true | es |
mods.originInfo.place | Instituto Multidisciplinario de Biología Celular | es |
sedici.subtype | Articulo | es |
sedici.rights.license | Creative Commons Attribution-NonCommercial-ShareAlike 4.0 International (CC BY-NC-SA 4.0) | |
sedici.rights.uri | http://creativecommons.org/licenses/by-nc-sa/4.0/ | |
sedici.description.peerReview | peer-review | es |
sedici.relation.journalTitle | Biophysical Journal | es |
sedici.relation.journalVolumeAndIssue | vol. 102, no. 12 | es |
sedici.rights.sherpa | * Color: amarillo* Pre-print del autor: si* Post-print del autor: restricted* Versión de editor/PDF:no* Condiciones:>>Author's pre-prints on private websites only>>Author's post-print on non-commercial hosting platforms including institutional repositories>>Debe ir enlazado a la versión de editor>>Deben reconocerse el copyright y la fuente editorial>>La versión de editor/PDF no puede utilizarse>>Publisher last contacted on 05/08/2015* Link a Sherpa: http://sherpa.ac.uk/romeo/issn/0006-3495/es/ |