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dc.contributor.advisorFernández Fernández, María del Rosario
dc.contributor.advisorValpuesta Moralejo, Jose María
dc.contributor.authorGragera Cabezudo, Marcos
dc.contributor.otherUAM. Departamento de Biología Moleculares_ES
dc.contributor.otherCSIC. Centro Nacional de Biotecnología (CNB)es_ES
dc.date.accessioned2020-09-14T13:29:17Z
dc.date.available2020-09-14T13:29:17Z
dc.date.issued2020-01-31
dc.identifier.urihttp://hdl.handle.net/10486/691892
dc.descriptionTesis doctoral inédita leída en la Universidad Autónoma de Madrid, Facultad de Ciencias, Departamento de Biología Molecular. Fecha de lectura:31-01-2020es_ES
dc.descriptionEsta tesis tiene embargado el acceso al texto completo hasta el 31-07-2021es_ES
dc.description.abstractEukaryotic cells have developed regulated pathways to maintain a fine balance between protein synthesis, folding, trafficking and degradation (proteostasis). Disruption of this homeostasis network may lead to the onset of pathologies such as cancer or neurodegenerative disorders. Therefore, cells count on several pathways to remove and prevent accumulation and aggregation of potentially toxic proteins, namely the ubiquitin-proteasome system (UPS) and autophagy. Three types of autophagy have been described so far: chaperone-mediated autophagy (CMA), microautophagy and macroautophagy. The chaperone Hsp70 has a central role in all of them. In macroautophagy, Hsp70, in collaboration with other partners (CHIP, Bag3, HspB8), forms a complex that recognizes, ubiquitinates and delivers aggregate-prone proteins towards special locations in cells (aggresomes), for further degradation. This project focuses on the biophysical characterization of the HspB8:Bag3:Hsp70 complex and its components. HspB8, Bag3 and Hsp70 form a stable ternary complex in vitro, which we have studied by different biophysical techniques and also by standard electron microscopy (negative staining) and cryoelectron microscopy (cryoEM). Using cryoelectron tomography, we have analyzed the distribution of the ternary complex in the specimen grids, and have found a tendency of the complex not to distribute evenly within the ice layer, but in a single stratum probably the air-water interface. Using single particle analysis, a low-resolution map has been obtained by negative staining, which combined with crosslinking-mass spectrometry data, has allowed us to build a pseudo-atomic model of the ternary complex. Additionally, we have obtained by cryoEM a low-resolution 3D map where only the atomic models of Hsp70SBD and BAG:Hsp70NBD could be accommodated. The model supports the previously described bimodal character of the Bag3:Hsp70 interaction.en_US
dc.format.extent136 pag.es_ES
dc.format.mimetypeapplication/pdfes_ES
dc.language.isoengen_US
dc.subject.otherCélulas - Degeneración - Tesis doctoraleses_ES
dc.subject.otherHomeostasis - Alteración - Enfermedades degenerativas - Tesis doctoraleses_ES
dc.titleBiophysical characterization of a chaperone complex involved in macroautophagyen_US
dc.typedoctoralThesisen_US
dc.subject.ecienciaBiología y Biomedicina / Biologíaes_ES
dc.date.embargoend2021-07-31
dc.rights.ccReconocimiento – NoComercial – SinObraDerivadaes_ES
dc.rights.accessRightsopenAccessen_US
dc.authorUAMFernández Fernández, María Del Rosario (264492)
dc.facultadUAMFacultad de Ciencias


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