A study, published in the journal Molecular Cell, reveals the biophysical properties, allowing certain proteins to infect others. The scientists at the Stowers Institute for Medical Research have conducted the study. They have identified the physical basis for the spread of crooked proteins known as prions inside the cells.
Prions are the proteins that propagate themselves to other proteins by adopting distinct structural shapes. They are often associated with age-related neurodegenerative disorders like Alzheimer’s and Parkinson’s diseases. However, recent studies have found that prions are also significant for normal cellular processes including immune responses.
Prions are like salt crystals
In order to investigate that how does a protein form a prion, the researcher started their analysis from the very first event of prion formation. This step is known as nucleation. The research team designed a powerful innovative cell-based fluorescence assay called “Distributed Amphifluoric FRET (DAmFRET).” The assay aimed at determining the key biophysical properties of nucleation for the proteins expressed in baker’s yeast cells.
The key property that distinguishes the prions from other proteins is their ability to become super-saturated. Other proteins began to aggregate as soon as they are sufficiently concentrated inside cells. However, prion-forming proteins remained soluble. They only aggregated when very rare random fluctuations in a few molecules stimulated them to do so.
The researchers have described prions as salt crystals and nucleation is the first step to the crystallization/formation of these crystals. They suggest that prion-forming proteins eventually aggregate, but only in a very particular arrangement. This arrangement is spontaneous but occurs in rare cases.
Previous investigations of prions had been lacking in the quantitative assays. Thus, this study serves as the first research to successfully measure the frequency of nucleation as a function of protein concentration inside cells. The success is attributed to the DAmFRET assay used in the study.
The scientists are now approaching to investigate how nucleation happens for prion-like proteins that are responsible for Alzheimer’s and other brain diseases. The researchers of this study have been sharing the approach with scientists at other academic research centers. However, lack of equipment and throughput to use DAmFRET, in most of the labs, is what hinders the approach.
Proteins provide both the structural and functional support to catalyze almost all of the chemical reactions necessary for the survival. The three-dimensional shape of a protein is critical for its working. However, a prion protein transforms itself into a different shape, infecting the other proteins to adopt the alternate shape.
The accumulation of prions in cells and tissues disrupt the normal functions, leading to diseases. However, in some cases, prion self-assemblies are essential for the normal functioning of the cells as well.
This study enumerates the physical basis for the transformation of proteins into prions. Moreover, the assay used in the study distinguishes between proteins that exhibit prion behavior and those that do not. In this way, the researchers would understand more about prions associated with diseases along with the prions involved in normal biological processes.