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dc.contributor.authorBacarizo, Julio
dc.contributor.authorMartínez Rodríguez, Sergio 
dc.contributor.authorMartín-García, José Manuel
dc.contributor.authorAndújar-Sánchez, Montserrat
dc.contributor.authorOrtiz-Salmerón, Emilia
dc.contributor.authorNeira, José Luis
dc.contributor.authorCámara-Artigas, Ana
dc.date.accessioned2015-02-17T10:49:24Z
dc.date.available2015-02-17T10:49:24Z
dc.date.issued2014
dc.identifier.citationBacarizo, J.; et al. Electrostatic Effects in the Folding of the SH3 Domain of the c-Src Tyrosine Kinase: pH-Dependence in 3D-Domain Swapping and Amyloid Formation. Plos One, 9(12): e113224 (2014). [http://hdl.handle.net/10481/34836]es_ES
dc.identifier.issn1932-6203
dc.identifier.urihttp://hdl.handle.net/10481/34836
dc.description.abstractThe SH3 domain of the c-Src tyrosine kinase (c-Src-SH3) aggregates to form intertwined dimers and amyloid fibrils at mild acid pHs. In this work, we show that a single mutation of residue Gln128 of this SH3 domain has a significant effect on: (i) its thermal stability; and (ii) its propensity to form amyloid fibrils. The Gln128Glu mutant forms amyloid fibrils at neutral pH but not at mild acid pH, while Gln128Lys and Gln128Arg mutants do not form these aggregates under any of the conditions assayed. We have also solved the crystallographic structures of the wild-type (WT) and Gln128Glu, Gln128Lys and Gln128Arg mutants from crystals obtained at different pHs. At pH 5.0, crystals belong to the hexagonal space group P6522 and the asymmetric unit is formed by one chain of the protomer of the c-Src-SH3 domain in an open conformation. At pH 7.0, crystals belong to the orthorhombic space group P212121, with two molecules at the asymmetric unit showing the characteristic fold of the SH3 domain. Analysis of these crystallographic structures shows that the residue at position 128 is connected to Glu106 at the diverging β-turn through a cluster of water molecules. Changes in this hydrogen-bond network lead to the displacement of the c-Src-SH3 distal loop, resulting also in conformational changes of Leu100 that might be related to the binding of proline rich motifs. Our findings show that electrostatic interactions and solvation of residues close to the folding nucleation site of the c-Src-SH3 domain might play an important role during the folding reaction and the amyloid fibril formation.es_ES
dc.description.sponsorshipThis research was funded by the Spanish Ministry of Science and Innovation and Ministry of Economy and Competitiveness and FEDER (EU): BIO2009-13261-C02-01/02 (ACA); BIO2012-39922-C02-01/02 (ACA); CTQ2013-4493 (JLN) and CSD2008-00005 (JLN); Andalusian Regional Government (Spain) and FEDER (EU): P09-CVI-5063 (ACA); and Valentian Regional Government (Spain) and FEDER (EU): Prometeo 2013/018 (JLN). Data collection was supported by European Synchrotron Radiation Facility (ESRF), Grenoble, France: BAG proposals MX-1406 (ACA) and MX-1541 (ACA); and ALBA (Barcelona, Spain) proposals 2012010072 (ACA) and 2012100378 (ACA).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.subjectCrystal structurees_ES
dc.subjectMolecular structure es_ES
dc.subjectProtein structurees_ES
dc.subjectTyrosinees_ES
dc.subjectOligomerses_ES
dc.subjectNucleationes_ES
dc.subjectFluorescence es_ES
dc.subjectProtein domainses_ES
dc.titleElectrostatic Effects in the Folding of the SH3 Domain of the c-Src Tyrosine Kinase: pH-Dependence in 3D-Domain Swapping and Amyloid Formationes_ES
dc.typejournal articlees_ES
dc.rights.accessRightsopen accesses_ES
dc.identifier.doi10.1371/journal.pone.0113224


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