Artículo
Truncation of a β-barrel scaffold dissociates intrinsic stability from its propensity to aggregation
Fecha de publicación:
11/2012
Editorial:
Cell Press
Revista:
Biophysical Journal
ISSN:
0006-3495
Idioma:
Inglés
Tipo de recurso:
Artículo publicado
Clasificación temática:
Resumen
Δ98Δ is a functional all-β sheet variant of intestinal fatty acid binding protein (IFABP) that was generated by controlled proteolysis. This framework is useful to study the molecular determinants related to aggregation of β-barrel proteins. Albeit displaying increased conformational plasticity, Δ98Δ exhibits a nativelike β-barrel topology and is able to support a cooperative folding behavior. Here we present a comparative study of IFABP and Δ98Δ regarding their conformational perturbation and aggregation propensity triggered by trifluoroethanol. Both proteins share a common nucleation-elongation mechanism, whereby the rate-limiting step is the formation of stable dimeric nuclei followed by the association of monomers to the growing aggregates. Despite leading to a less stable structure, the extensive truncation of IFABP yields a form exhibiting a somewhat lower tendency to aggregate. This finding appears at odds with the established notion that a perturbation of the native compact fold should necessarily favor the population of aggregation-prone species. In addition to the aggregation propensity dictated by a given amino-acid sequence, our contention holds that long-range interactions might also play a major role in determining the overall aggregation propensity. © 2012 Biophysical Society.
Palabras clave:
Barril Beta
,
Agregacion
,
Tfe
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Identificadores
Colecciones
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
Curto, Lucrecia María; Angelani, Carla Romina; Caramelo, Julio Javier; Delfino, Jose Maria; Truncation of a β-barrel scaffold dissociates intrinsic stability from its propensity to aggregation; Cell Press; Biophysical Journal; 103; 9; 11-2012; 1929-1939
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