Through computational analysis, researchers Salvador Ventura and Virg?­nia 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 researchers coincides with those obtained by researchers at Cambridge University, who also published similar data in the journal Proceedings of the National Academic of Sciences.

In the future UAB researchers are planning to expand their computational analysis to cover the whole set of human proteins with a defined 3D-structure. With this objective they seek to discover the proteins responsible for different genetic diseases of unknown origins and offer a series of new therapeutic targets for these disorders.

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