Researchers have found that replacing specific amino acids in polyglutamine peptides alters the pathways by which these peptides aggregate, causing them to form amyloid nanospheres. These nanospheres could be used for studying amyloid-induced toxicity in neurological disorders1 .
The researchers synthesised two polyglutamine peptides — one containing positively charged lysine and the other negatively charged glutamate. They probed the aggregation pathways of these polypeptides, both separately and in a mixture, in solutions of phosphate-buffered saline maintained at 37 degrees Celsius.
Imaging revealed that when allowed to aggregate separately, the lysine-containing polypeptides formed tape-like fibres and the glutamate-containing polypeptides formed fibre bundles. In contrast, when mixed, both polypeptides formed amyloid-like nanospheres. The researchers attribute this nanosphere formation to an intermolecular salt bridge that forms due to the interaction between lysine and glutamate.
The scientists found that changing the pH levels of the solutions disrupted the formation of nanospheres. In an acidic solution, the glutamate lost its interaction with the lysine, destroying the salt bridge, whereas in a slightly alkaline solution, a salt bridge formed, leading to nanosphere formation.
“This study would help tweak the fibre-forming paths that could spawn amyloid structures of different shapes and strengths,” says lead researcher Ashwani Thakur from the Indian Institute of Technology, Kanpur.
