2020 年 30 巻 1 号 p. 12-19
In this article, I introduce an analytical method named CS-PCA and its application for the destabilization mechanism of familial disease mutant of an amyloidogenic protein, β2-Microglobulin (β2m). Pressure concurrently induces several kinds of conformational changes of protein. We previously demonstrated that CS-PCA successfully decompose high-pressure NMR data, which contains mixed chemical shift data from these contributions, into individual contributions. Then, we applied this procedure in combination with MD simulation for the destabilization mechanism of the β2m mutant. Our approach revealed that the mutation induced the loosening of the inter-sheet packing and the network of correlated dynamics among some residues is relevant to the stability of inter-sheet packing.
