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Mechanism related to the onset of various genetic diseases revealed
Date:9/17/2009

hich are in the risk of becoming aggregated and these eventually form toxic assemblies. Globular proteins are known to be linked to hepatic, cardiac, renal and neurological disorders. However scientists do not know exactly how they manage to aggregate despite the fact that they are correctly folded within the body.

Through computational analysis, researchers Salvador Ventura and Virgnia Castillo, from the UAB Department of Biochemistry and Molecular Biology, have discovered that, in non-disease conditions, globular proteins related to conformational diseases are found associated in pairs to other proteins or in complex subunits, in a way that one protein covers the aggregation-prone region of the other and thus prevents the onset of this process. Therefore these regions remain obscured in the interior of the structure and are inoffensive to the organism as long as the two proteins are joined together. Researchers have found that genetic mutations produced in the interaction sites of the protein pair prevents their association, leaving aggregation-prone regions uncovered and favouring the formation of toxic aggregates. According to researchers, this would explain why out of two people with the same globular proteins and the same risk regions, only the one who suffers a genetic mutation would finally develop a disease.

The conclusions obtained have led researchers to contemplate the possibility that dissociation is a general mechanism, which not only affects globular proteins with a clearly defined structure, but also others which have not yet been characterised and which could be the cause of diseases of unknown origin.

As possible strategies to prevent the dissociation of proteins, the authors propose introducing genetic mutations into the proteins to strengthen their association and developing specific molecules to block the risk regions of already dissociated proteins.

The results of the study carried out by UAB researcher
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Contact: Mara Jess Delgado
MariaJesus.Delgado@uab.cat
34-935-814-049
Universitat Autonoma de Barcelona
Source:Eurekalert

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