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dc.contributor.author
Tsytlonok, Maksym
dc.contributor.author
Craig, Patricio Oliver
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dc.contributor.author
Sivertsson, Elin
dc.contributor.author
Serquera, David
dc.contributor.author
Perrett, Sarah
dc.contributor.author
Best, Robert B.
dc.contributor.author
Wolynes, Peter G.
dc.contributor.author
Itzhaki, Laura S.
dc.date.available
2016-09-23T17:53:59Z
dc.date.issued
2013-11
dc.identifier.citation
Tsytlonok, 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.identifier.issn
0969-2126
dc.identifier.uri
http://hdl.handle.net/11336/7694
dc.description.abstract
Here, 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.format
application/pdf
dc.language.iso
eng
dc.publisher
Cell Press
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dc.rights
info:eu-repo/semantics/openAccess
dc.rights.uri
https://creativecommons.org/licenses/by-nc-nd/2.5/ar/
dc.subject
Heat Repeat
dc.subject
Folding Mechanism
dc.subject
Pr65
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Molecular Simulation
dc.subject.classification
Biofísica
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dc.subject.classification
Ciencias Biológicas
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dc.subject.classification
CIENCIAS NATURALES Y EXACTAS
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dc.title
Complex Energy Landscape of a Giant Repeat Protein
dc.type
info:eu-repo/semantics/article
dc.type
info:ar-repo/semantics/artículo
dc.type
info:eu-repo/semantics/publishedVersion
dc.date.updated
2016-09-05T13:12:36Z
dc.journal.volume
21
dc.journal.number
11
dc.journal.pagination
1954-1965
dc.journal.pais
Países Bajos
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dc.journal.ciudad
Amsterdam
dc.description.fil
Fil: Tsytlonok, Maksym. University Of Cambridge; Estados Unidos. Hutchison/MRC Research Centre; Reino Unido
dc.description.fil
Fil: 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.description.fil
Fil: Sivertsson, Elin. University Of Cambridge; Reino Unido
dc.description.fil
Fil: Serquera, David. Hutchison/MRC Research Centre; Reino Unido
dc.description.fil
Fil: Perrett, Sarah. Chinese Academy Of Sciences; República de China
dc.description.fil
Fil: Best, Robert B.. University Of Cambridge; Reino Unido
dc.description.fil
Fil: Wolynes, Peter G.. Rice University; Estados Unidos
dc.description.fil
Fil: Itzhaki, Laura S.. University Of Cambridge; Reino Unido
dc.journal.title
Structure With Folding & Design.
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dc.relation.alternativeid
info:eu-repo/semantics/altIdentifier/url/http://www.sciencedirect.com/science/article/pii/S096921261300350X
dc.relation.alternativeid
info:eu-repo/semantics/altIdentifier/doi/http://dx.doi.org/10.1016/j.str.2013.08.028
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