| Affiliation: | (1) Department of Biological Chemistry, The Johns Hopkins University School of Medicine, 725 N. Wolfe street, 21205 Baltimore, Maryland, USA;(2) Department of Material and Life Science, Graduate School of Engineering, Osaka University and PRESTO, Japan Science and Technology Agency (JST), 2-1 Yamadaoka, 565-0871 Osaka, Suita, Japan |
| Abstract: | In amyloid related diseases, proteins form fibrillar aggregates with highly ordered  -sheet structure regardless of their native conformations. Formation of such amyloid fibrils can be reproducible in vitro using isolated proteins/peptides, suggesting that amyloid fibril formation takes place as a result of protein conformational change. In vitro studies revealed that perturbation of the native structure is important for the fibril formation, and it is suggested that the mechanisms of amyloid fibril formation share the mechanisms of protein folding. In particular, amyloid fibril formation is similar to one of the common features of proteins, i.e. amorphous aggregation upon partial unfolding, which is likely driven by hydrophobic interactions through exposed protein interior. However, these molecular associations are distinct phenomena, and identifying factors that lead to amyloid fibril formation would precede our understanding of the mechanisms of amyloid fibrillization. The necessity of understanding the nature of protein denatured states is also suggested.Received 6 July 2003; accepted 19 August 2003 |
