School of Pharmacy

How protein molecules aggregate to form fibres

The Laboratory of Biophysics and Surface Analysis published the following article in The Biophysical Journal:

Insulin Fibril Nucleation: The Role of Prefibrillar Aggregates

M. I. Smith*, J. S. Sharp*,1 and C. J. Roberts 1,2

* School of Physics and Astronomy

1.Nottingham Nanotechnology and Nanoscience Centre

2. Laboratory of Biophysics and Surface Analysis, School of Pharmacy and Nottingham Nanotechnology and Nanoscience Centre, The University of Nottingham, Nottingham, United Kingdom

Lay summary:

The aggregation of protein molecules into long fibrils is a property of many proteins when they become damaged or denatured. Such aggregates are formed as part of the pathology of many diseases, including Alzheimer’s Disease and Parkinson’s Disease. It is very important therefore to understand the fundamental reasons why proteins form such structures. Such understanding may eventually lead to therapies based upon interfering with the growth of the protein fibres.

In this paper we have used biophysical techniques to study the formation of early stage fibrillar aggregates and fibrils of insulin at 60°C and under acid conditions. The speed of disintegration of the aggregates was also studied. These experiments reveal that formation of prefibrillar aggregates is reversible under the solution conditions studied and show that it is possible to significantly reduce the nucleation times associated with the beginnings of fibril growth in insulin solutions by increasing the concentration of prefibrillar aggregates in solution. These results provide convincing evidence that less structured prefibrillar aggregates can act as fibril-forming intermediates on the path to the formation of mature fibres.

Click on the title of the publication to see the abstract and full detail

School of Pharmacy

University of Nottingham
University Park
Nottingham, NG7 2RD

For all enquiries please visit:
www.nottingham.ac.uk/enquiry