Small molecules called osmolytes help proteins maintain their structure and function under stressful conditions, a recent study suggests, providing an important insight that could aid in the development of treatments for diseases such as Alzheimer's and Parkinson's.
Osmolytes are small molecules that help cells survive stress by stabilizing proteins and preventing them from misfolding. Misfolded proteins cannot function properly, leading to diseases. Osmolytes are important in maintaining the stability of protein structures, making them potential targets for new drugs.
A research team led by Dr. Shubhasis Halder and his student Deep Chowdhary at the S.N. Bose National Centre for Basic Sciences, an autonomous institute of the Department of Science and Technology, used a technique called covalent magnetic forceps to observe how individual protein molecules bind and unfold under different conditions and then interact with osmolytes.
They focused on a protein called protein L and tested its interaction with two osmolytes – trimethylamine N-oxide (TMAO) and trehalose. At high concentrations, TMAO greatly increased the ability of protein L to bind, making it more resistant to misbinding.
At low concentrations (up to 1M), TMAO had little effect on the protein's opening force. However, at higher concentrations (1.5M), the opening force increased significantly, indicating that TMAO interacts with the bound state of protein L. This indicates that TMAO interacts with the protein in a way that helps it bind and remain stable. High levels of TMAO are linked to heart disease, so knowing how it interacts with proteins could lead to better treatments.
