Artículo
Complex Energy Landscape of a Giant Repeat Protein
Tsytlonok, Maksym; Craig, Patricio Oliver
; Sivertsson, Elin; Serquera, David; Perrett, Sarah; Best, Robert B.; Wolynes, Peter G.; Itzhaki, Laura S.

Fecha de publicación:
11/2013
Editorial:
Cell Press
Revista:
Structure With Folding & Design.
ISSN:
0969-2126
Idioma:
Inglés
Tipo de recurso:
Artículo publicado
Clasificación temática:
Resumen
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.
Palabras clave:
Heat Repeat
,
Folding Mechanism
,
Pr65
,
Molecular Simulation
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Articulos(IQUIFIB)
Articulos de INST.DE QUIMICA Y FISICO-QUIMICA BIOLOGICAS "PROF. ALEJANDRO C. PALADINI"
Articulos de INST.DE QUIMICA Y FISICO-QUIMICA BIOLOGICAS "PROF. ALEJANDRO C. PALADINI"
Citación
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
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