Aug 21, 2006
Checking up on protein structure formation
In the test-tube, many proteins will aggregate to form insoluble needle-shaped structures called fibrils. A small number of proteins can also aggregate in the brain, leading to dementia diseases such as Alzheimer's and Parkinson's.
There is growing consensus that the cytotoxic species in the aggregation process is a ring-shaped oligomer which forms early in the process and binds to and permeabilizes the membranes of neuronal cells.
Now scientists at the Interdisciplinary Nanoscience Center iNANO in Denmark - which is run jointly by Aarhus University and Aalborg University - have identified an early and a mature state of such an oligomer, shedding further light on the formation of this elusive species. They described their research in Nanotechnology.
Using the 29-residue peptide hormone glucagon from Novo Nordisk A/S as a model system, the scientists found that a few hours of incubation led to the formation of doughnut-shaped structures with a hole in the middle. These structures later filled out to form a more solid disc. And the solid disc appears to be the precursor for the needle-shaped fibrils.
The scientists hope that more information about how these oligomers form and change to other structures may allow them to understand how to control and prevent their formation, and thus ultimately stop the progression of dementia.
About the author
Flemming Besenbacher is head of the Interdisciplinary Nanoscience Center at the University of Aarhus and Aalborg University, and a professor in the department of physics and astronomy at the University of Aarhus. Daniel Otzen is professor of biophysics at Aalborg University. His research group uses spectroscopic techniques to study protein folding and stability with particular focus on the conformational changes associated with protein aggregation and fibrillation.