doi:10.1038/nindia.2016.129 Published online 29 September 2016
Researchers have gained new insights into the formation of amyloid fibrils that slowly destroy nerve cells in degenerative diseases such as Alzheimer’s by studying the unfolding of a hen egg-white protein1.
These revelations will help with developing therapies to check the progress of degenerative diseases by stopping amyloid fibril formation.
Amyloid fibrils cause more than 20 degenerative diseases. To understand how they form researchers use urea that is known to unfold proteins, but how it unfolds proteins is not yet clearly understood.
To get a better idea about this process, the researchers dissolved hen egg-white protein lysozyme in solutions containing urea for 2 to 10 hours and more than 10 hours. Using X-ray diffraction experiments, they then mapped urea-protein interaction.
The urea molecules bound to the protein surface in a phased manner, displacing water molecules. The urea molecules first latched on to the backbone and later to side chains of the proteins through forming hydrogen bonds and van der Waals interaction, an attractive force that is weaker than chemical bonds.
This eventually allowed the urea molecules to break a few intra-protein hydrogen bonds, causing the protein molecules to unfold. This atomic-level picture of protein unfolding may be useful for finding novel therapies for various degenerative diseases, say the researchers.
1. Raskar, T. et al. Time-dependent X-ray diffraction studies on urea/hen egg white lysozyme complexes reveal structural changes that indicate onset of denaturation. Sci. Rep. (2016) doi: 10.1038/srep32277