‘For the first time, scientists have identified the structure of a protein fibre linked to early-onset type 2 diabetes.
Scientists compared the wild type of amylin fibrils and compared it with S20G, the genetic variants found in people with early-onset type 2 diabetes. The fibrils formed by the wild-type and S20G versions of amylin were different. Wild-type fibrils had two copies of amylin per rung, whereas a form of the S20G fibrils had three amylin fibrils per layer.
The study results suggest:
Fibrils can form templates onto which more copies of amylin can lock. S20G-variant protein aggregates more quickly and is linked to the more rapid onset of type 2 disease.
Neil Ranson, Professor of Structural Molecular Biology and Deputy Director of the Astbury Centre for Structural Molecular Biology at the University of Leeds, co-led the project. He said: “This is a really exciting result because it reveals a mechanism for how ever-larger aggregates might form and that is crucial in understanding the disease process. We know this happens in disease but we have never understood clearly how it happens. Now with these structures we’re getting the first glimpse what might be going on.”
Sheena Radford FRS, Astbury Professor of Biophysics and Director of the Astbury Centre and co-lead for the study, added: “We know that the S20G protein aggregates more quickly, and this study provides the rationale as to why that might be the case. This is important, not just for understanding amylin – but for understanding many amyloid diseases in which run-away fibril formation occurs. This is just the beginning of the journey to find new ways of combatting amyloid disease and was impossible before the new powerful methods of electron microscopy were developed.”