How does the body protect itself from harmful proteins?

Defective proteins are recognized and eliminated by the body
Against much looming damage, our body has developed protective mechanisms based on natural processes that usually work relatively efficiently. These include, for example, the disposal of defective, in the worst case toxic proteins. Scientists at the Charité - Universitätsmedizin Berlin have now deciphered how the disposal of defective proteins, which is essential for the survival of a cell is fundamental. This could also open up new therapeutic options, for example in the field of neurodegenerative diseases, the researchers report.

The Charité scientists have found out by themselves how two special auxiliary proteins make it possible to eliminate defective proteins. They report in the journal "Nature Communications", as the defective messenger ribonucleic acid, which serves as a "blueprint" of protein biosynthesis, recognized and their degradation is initiated. The two "rescue proteins" virtually eliminate potentially harmful compounds, which could also open up new options for the treatment of certain diseases, the researchers report.

The ribosomes read the information from the mRNA and form corresponding proteins. Defective mRNA must therefore be eliminated so that no harmful proteins arise. (Image: designua / fotolia.com)

Protein biosynthesis accurately analyzed
The research team around Dr. According to Tarek Hilal of the Institute of Medical Physics and Biophysics of the Charité, genetic information stored in the genes during protein biosynthesis is read out by the so-called ribosome and converted into proteins (proteins). For this purpose, the information stored in the chromosomes first translated into a mobile form, the so-called messenger ribonucleic acid (mRNA), which can then be read the ribosome and then serves as an exact blueprint for the production of proteins. A defective mRNA results in the production of defective, potentially harmful proteins, which is why it must be efficiently recognized and degraded, the researchers emphasize.

Defective mRNA blocks the ribosomes
In the current study, the researchers used "mRNAs without stop signal" to investigate which mechanisms are used here in the body to eliminate the defective messenger ribonucleic acid. If the "non-stop mRNAs" are read from the ribosome, the entire process stagnates and the orderly termination of protein biosynthesis remains, the researchers explain the effect of the defective mRNA. As a result, the ribosome can not perform any further actions and remains blocked.

Auxiliary proteins dissolve blockages
Using so-called cryo-electron microscopy, the researchers analyzed the structure of the blocked compounds from ribosomes and mRNA and they were able to detect the specific auxiliary proteins (Dom34 and Hbs1) such locked ribosomes and initiate the dissolution of the blocked complexes and the degradation of mRNA, report the Charité scientists. The two helper proteins would only tapped conserved areas of the ribosome, which are typically occupied by mRNA, the experts further explain. This competitive binding mode ensures that only ribosomes are attacked by defective mRNAs.

Hope for new therapeutic options
Study Director Tarek Hilal emphasizes that "research into the effects of defective mRNAs and the consequences of a lack of degradation is becoming increasingly important". In particular, in neurodegenerative diseases such as amyotrophic lateral sclerosis (ALS), erroneous mRNAs are detected and a "molecular understanding of the cellular control mechanisms can therefore be helpful to find starting points for therapeutic purposes," the expert said. (Fp)