The Landscape of the Prion Protein's Structural Response to Mutation Revealed by Principal Component Analysis of Multiple NMR Ensembles
Figure 1
PCA analysis on 11 hPrP structures reveal structural perturbations correlated with prion disease.
(A) Projection of hPrP NMR ensembles onto PC1 and PC2. (B) Projection of hPrP NMR ensembles onto PC1 and PC3. For (A) and (B), each point on the conformer plot represents an NMR model, and the models are colored to reflect NMR ensembles. For each NMR ensemble, the NMR representative model that has been selected by OLDERADO [39] is indicated by a black triangle. Ovals indicate dominant clusters that represent the hPrP diseases of CJD (green oval), FFI (blue oval), GSS (red oval), as well as the set of WT and variant proteins (WT+V, black oval). The ovals representing hPrP disease are also labeled, with the PDB code of their corresponding NMR ensemble in brackets. 2K1D models which cluster separately from the rest of the 2K1D ensemble are circled (dashed brown oval). (C) Eigenvalue contribution of PCs to variance of the dataset. Further analysis of this dataset is demonstrated in Figure 4A.