The world’s first tool capable of identifying the proteins that trigger amyloidosis in humans

Geneticists have developed the world’s first tool to identify the proteins that form amyloid aggregates.

An international team has developed the first software to estimate protein pairs in amyloid fibrils capable of coaggregation, a process by which proteins bind to each other and become toxic to the brain through amyloid deposits.

In their study, published in the journal Journal of Molecular Biology – JMB the tool showed an accuracy of over 94%.

Amyloids are protein aggregates associated with a number of serious and incurable diseases, such as Alzheimer’s, Parkinson’s and Huntington’s, to name just a few.

The presence of amyloids is not always pathological; many of them having functional, beneficial roles in cells.

What can trigger aggregation into amyloid fibrils are changes in protein structure, scientists say. Soluble proteins aggregate together becoming insoluble and toxic to the human body.

However, in recent years, a considerable amount of data has been accumulated on the coaggregation of the various proteins that form amyloid plaques.

The team of specialists in genetics and biotechnology from the universities of St. Petersburg (Russia) and Montpellier (France) is the first in the world to propose a bioinformatics tool, AmyloComp, to identify pairs of proteins capable of coaggregation – of binding together .

The software is written in the Python programming language and is available as an online application.

“Normally, amyloid fibrils are made up of multiple copies of the same protein. In this case, they are homogeneous and have the same structure. However, what we are trying to discover is the co-aggregation of different proteins into a common fibril, that is, the stacking of different proteins within the same amyloid fibril,” said Stanislav Bondarev, co-author of the study, professor at the Department of Genetics and Biotechnology of the University of Saint Petersburg.

According to him, the AmyloComp software developed by university researchers has demonstrated over 94% accuracy on a model data set and also reliably classifies known positive and negative examples of protein co-aggregation.

Protein coaggregation can play various biological roles in the body.

On the one hand, the “amyloid cascade” hypothesis was proposed quite some time ago. The hypothesis is that pathological amyloid aggregates can trigger the aggregation of other proteins.

On the other hand, some important biological processes require the coagulation of various amyloid-forming proteins. Among known examples of coaggregation are the human proteins RIPK1 and RIPK3. This co-aggregation is part of the signaling cascade to trigger the antiviral response.

AmyloComp software can identify similar examples at the proteome scale.

The bioinformatics tool is unique, as other similar approaches do not model the co-aggregation of two amyloid proteins.

The method developed by researchers from St. Petersburg University is based on a comparison of the amino acid sequence of two proteins and takes into account the possibility of overlapping of different proteins within the same amyloid fibril. This approach makes it possible to identify different sequences that form a single structure.

It can be applied to identify proteins capable of triggering amyloidosis in humans.

AmyloComp, Abstract graph. Credit Journal of Molecular Biology, April 2024