IQUIFIB   02644
INSTITUTO DE QUIMICA Y FISICOQUIMICA BIOLOGICAS "PROF. ALEJANDRO C. PALADINI"
Unidad Ejecutora - UE
congresos y reuniones científicas
Título:
Conformation coalescence of β-barrel proteins at sub-aggregating concentrations of TFE mimics the formation of aggregation prone species
Autor/es:
ANGELANI, C.R.; CARAMELO, J.J.; DELFINO J.M.; CURTO L.M.
Lugar:
Carlos Paz, Córdoba
Reunión:
Congreso; . XLII Reunión Anual de la Sociedad Argentina de Biofísica (SAB).; 2013
Resumen:
Δ98Δ and Δ78Δ are two functional all-β sheet variants of IFABP (intestinal fatty acid binding protein), being useful models to study the determinants related to aggregation of β-barrel proteins. Albeit displaying increased conformational plasticity, these variants exhibit a native-like β-barrel topology and are able to support a cooperative folding. Interestingly, while IFABP and Δ98Δ are monomers, Δ78Δ is dimeric. These proteins share a common nucleation-elongation mechanism of aggregation, where the rate-limiting step is the formation of dimeric nuclei. A straightforward correlation between their intrinsic stability (IFABP≥Δ78Δ>Δ98Δ) with their aggregation propensity (Δ78Δ>IFABP≥Δ98Δ) cannot be established. This observation appears at odds with the established notion that perturbations of the native fold necessarily favor the population of aggregation-prone species. To understand the early events leading to the formation of the critical nucleus, the initial conformational changes occurring after the addition of an aggregating inducing co-solvent were examined (25 % v/v TFE). The spectral changes in the far and near UV CD were measured immediately after diluting the protein in TFE. Interestingly, the CD spectra for each of the proteins revealed the coalescence of all three proteins into conformations richer in β content. The same behavior was observed when incubating at sub-aggregating concentrations of TFE (≤ 10%v/v). In this scenario, low concentrations of co-solvent might produce conformational changes similar to those leading to the aggregation prone species. This approach might help in understanding the early conformational changes controlling the onset of aggregation.