Detailed Analysis of the Energy Barriers for Amyloid Fibril Growth

Authors


  • A.K.B. thanks Magdalene College for support through a research fellowship. We acknowledge support from the Wellcome (C.M.D., T.P.J.K.) and Leverhulme (C.M.D.) Trusts. We thank Novonordisk, Denmark, for a generous gift of glucagon, Vittorio Bellotti for providing β2-microglobulin, and Sarah Perrett for supplying the Ure2p (from Saccharomyces cerevisiae) protein. We thank David Chandler for helpful discussions.

Abstract

original image

The free energy barriers that determine the kinetics of the growth of amyloid fibrils have been measured for a series of peptides and proteins using a quartz crystal microbalance. The results indicate that the enthalpic contribution to the free energy barrier is invariably unfavorable and correlates with the size and structure of the soluble parent polypeptide, whereas the entropic contribution is favorable and linked to the hydrophobicity of the peptide sequence.

Ancillary