Truncation of a ß-barrel scaffold dissociates intrinsic stability from its propensity to aggregation.
Biophys J
; 103(9): 1929-39, 2012 Nov 07.
Article
em En
| MEDLINE
| ID: mdl-23199921
Δ98Δ is a functional all-ß 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 ß-barrel proteins. Albeit displaying increased conformational plasticity, Δ98Δ exhibits a nativelike ß-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.
Texto completo:
1
Coleções:
01-internacional
Base de dados:
MEDLINE
Assunto principal:
Deleção de Sequência
/
Dobramento de Proteína
/
Proteínas de Ligação a Ácido Graxo
/
Multimerização Proteica
Limite:
Animals
Idioma:
En
Revista:
Biophys J
Ano de publicação:
2012
Tipo de documento:
Article
País de afiliação:
Argentina
País de publicação:
Estados Unidos