IQUIFIB   02644
INSTITUTO DE QUIMICA Y FISICOQUIMICA BIOLOGICAS "PROF. ALEJANDRO C. PALADINI"
Unidad Ejecutora - UE
congresos y reuniones científicas
Título:
ON THE PROPENSITY OF Β BARRELS TO YIELD AMYLOID AGGREGATES
Autor/es:
CURTO L.M.; ANGELANI, C.R.; CABANAS, I.S; CARAMELO, J.J.; DELFINO J.M.
Lugar:
La Plata, Buenos Aires
Reunión:
Congreso; 8th International Conference on Lipid Binding Proteins.; 2013
Resumen:
The genesis of protein fibrils underlies both functional cell phenomena as well as aberrant disease-related polymerization. Understanding this self-assembly process remains a key challenge in biology. Particularly, a diverse array of polypeptides yields amyloid cross-β structure. In this context, the ?β-clam? of intestinal fatty acid binding protein (IFABP) and its variants Δ98Δ and Δ78Δ (29-126 and 29-106 stretches of IFABP, respectively) offer a unique opportunity for investigating the transition between these motifs. The abridged forms exhibit a plastic native-like β-barrel topology supporting cooperative folding. Whereas IFABP and Δ98Δ are monomers, Δ78Δ is a dimer in solution. Challenging these scaffolds with 25% v/v trifluoroethanol (TFE) readily triggers aggregation. The evolution of turbidity shows a common scaling behavior of the kinetics, pointing to a primary nucleation-elongation mechanism, whereby the stabilization of dimeric nuclei precedes the association of protein to the growing aggregates. Binding of dyes as well as TEM images suggest amyloid-like character. A consensus prediction for aggregation-prone peptides identifies the shared segment 58-71. Nevertheless, intrinsic stability does not follow a straightforward correlation with aggregation tendency. These facts appear at odds with the established notion that a perturbation of the native fold should necessarily favor the population of aggregation-prone species. Interestingly, exposure to sub-aggregating concentration of TFE reveals the coalescence of all three proteins into a conformation richer in β content and more akin in stability. All in all, overall aggregation propensity might not only depend on local amino acid sequence, but also on the persistence of key spatial interactions.