How cells beat the ‘fried-egg syndrome’
New research from the Hatters Lab, Dept of Biochemistry, published in PNAS this week.
In brain diseases such as Huntington’s and Alzheimer’s Disease, abnormal accumulations of protein aggregates or clumps are thought to be a central feature of these diseases.
Cells, enclosed by a fatty membrane contain many proteins, which do the ‘work’ of the cell. They catalyse chemical reactions, send messages to activate or inhibit certain functions within the cell, or simply provide structural support for cell movement and division. Under the microscope, you can see that it is definitely a tight squeeze within the cell, packing in a lot of proteins and organelles.
How is this possible? The ability of proteins to exist in soluble and solid ‘aggregated’ states, may provide a clue.
Professor Danny Hatters and his research group in the Bio21 Institute, Department of Biochemistry and Molecular Biology, School of Biomedical Sciences, had their research published in PNAS this week. Their work shows that the body’s cells have a way of regulating the solubility of their proteins which are densely packed inside the cell; floating or actively moving within the cell’s liquid ‘cytosol’.
“Balance is everything in life and the cell seeks to strike a balance between soluble and aggregated proteins depending on the type of stress they experience,” explains Professor Hatters.
“Normally proteins within the cell can exist in soluble, or aggregated solid form and switch between these states. However, sometimes aggregates form abnormally. This process is called ‘protein misfolding.’”
A good analogy of 'misfolding' is when you heat an egg in a pan. Within a few seconds the gelatinous clear egg white, which is full of protein, hardens into an opaque ‘egg white’. The heat has denatured the egg protein ‘ovalbumin’, resulting in a change in structure. If you were to observe these changes at the molecular level, you would see that the egg white protein, has changed its conformation and stuck to other ovalbumin molecules.
This change in the protein from a solution to a solid form is called aggregation. When this happens abnormally in brain cells, it is thought to be the cause of a number of neurodegenerative brain diseases, such as Huntington’s Disease, Alzheimer’s and Parkinson’s Disease.
Article orginally published by Bio21 Institute, 22 January 2020.