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dc.creatorTsytlonok, Maksym-
dc.creatorCraig, Patricio Oliver-
dc.creatorSivertsson, Elin-
dc.creatorSerquera, David-
dc.creatorPerrett, Sarah-
dc.creatorBest, Robert B.-
dc.creatorWolynes, Peter G.-
dc.creatorItzhaki, Laura S.-
dc.date2016-09-23T17:53:59Z-
dc.date2016-09-23T17:53:59Z-
dc.date2013-11-
dc.date2016-09-05T13:12:36Z-
dc.date.accessioned2019-04-29T15:50:32Z-
dc.date.available2019-04-29T15:50:32Z-
dc.date.issued2013-11-
dc.identifierTsytlonok, Maksym; Craig, Patricio Oliver; Sivertsson, Elin; Serquera, David; Perrett, Sarah; et al.; Complex Energy Landscape of a Giant Repeat Protein; Cell Press; Structure With Folding & Design.; 21; 11; 11-2013; 1954-1965-
dc.identifier0969-2126-
dc.identifierhttp://hdl.handle.net/11336/7694-
dc.identifier.urihttp://rodna.bn.gov.ar:8080/jspui/handle/bnmm/303459-
dc.descriptionHere, we reveal a remarkable complexity in the unfolding of giant HEAT-repeat protein PR65/A, a molecular adaptor for the heterotrimeric PP2A phosphatases. The repeat array ruptures at multiple sites, leading to intermediate states with noncontiguous folded subdomains. There is a dominant sequence of unfolding, which reflects a nonuniform stability distribution across the repeat array and can be rationalized by theoretical models accounting for heterogeneous contact density in the folded structure. Unfolding of certain intermediates is, however, competitive, leading to parallel unfolding pathways. The low-stability, central repeats sample unfolded conformations under physiological conditions, suggesting how folding directs function: certain regions present rigid motifs for molecular recognition, whereas others have the flexibility with which to broaden the search area, as in the fly-casting mechanism. Partial unfolding of PR65/A also impacts catalysis by altering the proximity of bound catalytic subunit and substrate. Thus, the repeat array orchestrates the assembly and activity of PP2A.-
dc.descriptionFil: Tsytlonok, Maksym. University Of Cambridge; Estados Unidos. Hutchison/MRC Research Centre; Reino Unido-
dc.descriptionFil: Craig, Patricio Oliver. Consejo Nacional de Investigaciones Científicas y Técnicas. Oficina de Coordinación Administrativa Parque Centenario. Instituto de Investigaciones Bioquimicas de Buenos Aires; Argentina. University Of California At San Diego; Estados Unidos-
dc.descriptionFil: Sivertsson, Elin. University Of Cambridge; Reino Unido-
dc.descriptionFil: Serquera, David. Hutchison/MRC Research Centre; Reino Unido-
dc.descriptionFil: Perrett, Sarah. Chinese Academy Of Sciences; República de China-
dc.descriptionFil: Best, Robert B.. University Of Cambridge; Reino Unido-
dc.descriptionFil: Wolynes, Peter G.. Rice University; Estados Unidos-
dc.descriptionFil: Itzhaki, Laura S.. University Of Cambridge; Reino Unido-
dc.formatapplication/pdf-
dc.formatapplication/pdf-
dc.languageeng-
dc.publisherCell Press-
dc.relationinfo:eu-repo/semantics/altIdentifier/url/http://www.sciencedirect.com/science/article/pii/S096921261300350X-
dc.relationinfo:eu-repo/semantics/altIdentifier/doi/http://dx.doi.org/10.1016/j.str.2013.08.028-
dc.rightsinfo:eu-repo/semantics/restrictedAccess-
dc.rightshttps://creativecommons.org/licenses/by-nc-nd/2.5/ar/-
dc.sourcereponame:CONICET Digital (CONICET)-
dc.sourceinstname:Consejo Nacional de Investigaciones Científicas y Técnicas-
dc.sourceinstacron:CONICET-
dc.subjectHeat repeat-
dc.subjectfolding mechanism-
dc.subjectPr65-
dc.subjectmolecular simulation-
dc.subjectBiofísica-
dc.subjectCiencias Biológicas-
dc.subjectCIENCIAS NATURALES Y EXACTAS-
dc.titleComplex Energy Landscape of a Giant Repeat Protein-
dc.typeinfo:eu-repo/semantics/article-
dc.typeinfo:eu-repo/semantics/publishedVersion-
dc.typeinfo:ar-repo/semantics/articulo-
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