Unknown

Dataset Information

0

Truncation of a ?-barrel scaffold dissociates intrinsic stability from its propensity to aggregation.


ABSTRACT: ?98? is a functional all-? 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 ?-barrel proteins. Albeit displaying increased conformational plasticity, ?98? exhibits a nativelike ?-barrel topology and is able to support a cooperative folding behavior. Here we present a comparative study of IFABP and ?98? 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.

SUBMITTER: Curto LM 

PROVIDER: S-EPMC3491725 | BioStudies | 2012-01-01

REPOSITORIES: biostudies

Similar Datasets

2017-01-01 | S-EPMC5302452 | BioStudies
2009-01-01 | S-EPMC2821277 | BioStudies
2018-01-01 | S-EPMC6121581 | BioStudies
2006-01-01 | S-EPMC2501113 | BioStudies
2009-01-01 | S-EPMC2762586 | BioStudies
2009-01-01 | S-EPMC2722364 | BioStudies
2015-01-01 | S-EPMC4658145 | BioStudies
1000-01-01 | S-EPMC3795488 | BioStudies
2016-01-01 | S-EPMC4748702 | BioStudies
2020-01-01 | S-EPMC7306164 | BioStudies