Structural and dynamical analysis of disease-related proteins by synchrotron radiation and neutron beam

Utilization of synchrotron radiation and neutron beam allows to investigate structural changes of biomolecules during the expression of biological functions, and molecular dynamics as a driving force of the structural changes. In amyloidosis such as Alzheimer's disease, deposition of amyloid fibrils, which are aggregates of the causative proteins, is a hallmark of the disease. It is known that some types of fibrils are more cytotoxic than other types of fibrils. Our recent study on a model protein has shown that 1) highly cytotoxic fibrils show enhanced atomic motions, 2) When they bind to phospholipid membranes (model of biomembranes), they caused a large disorder in the membrane structure while the content of antiparallel β-sheets increases in the fibrils, 3) less cytotoxic fibrils affect the membrane structure much less with structural changes of the fibrils in the opposite direction to the more cytotoxic fibrils. Part of the physical properties specific to highly cytotoxic fibrils are thus clarified. Another study using synchrotron radiation on the de novo oncoprotein NCYM has succeeded to reveal the details of its secondary structure, where α-helices and β-sheets are concentrated in the central part while other regions tend to be disordered, though there was no structural information on this protein before. Furthermore, our structural analysis of the complex of NCYM and a DNA aptamer which keeps NCYM in its active state has provided new information on how these two molecules interact upon complexation. In this paper, details of the above two research topics are introduced and discussed. (author)