Figure 10. Correlated chemical shift changes reveal the uncoupling of the intramolecular allosteric network in PKA-C^F100A.

(A) Comparison of the CHEmical Shift Covariance Analysis (CHESCA) matrices obtained from the analysis of the amide CS of PKA-C^WT (blue correlations) and PKA-C_F100A (black correlations). The correlations coefficients (R_ij) were calculated using the apo, ADP-, ATPγN-, and ATPγN/PKI_5-24-bound states. For clarity, only correlation with R_ij > 0.98 are displayed. For the enlarged CHESCA map of F100A see Figure 10—figure supplement 1. The data for the PKA-C^WT matrix were taken from Walker et al., 2019. (B) Community CHESCA analysis of PKA-C^WT (blue correlations) and PKA-C^F100A (black correlations). Only correlations with R_A,B > 0.98 are shown. (C) Spider plot showing the extent of intramolecular correlations identified by the community CHESCA analysis for PKA-C^F100A mapped onto the crystal structure (PDB: 4WB5). The thickness of each line in the spider plot indicates the extent of coupling between the communities.

Figure 10—figure supplement 1. Intermolecular allosteric network of F100A mapped using CHEmical Shift Covariance Analysis (CHESCA) and community CHESCA.

(A) CHESCA matrix obtained from the amide chemical shift trajectories of PKA-C^F100A in the apo, ADP-, ATPγN-, and ATPγN/PKI_5-24-bound states. Only correlations with R_ij > 0.98 are displayed. (B) Plot of the correlation scores versus residue calculated for PKA-C^WT (blue) and PKA-C^F100A (black). (C) Community CHESCA analysis of PKA-C^F100A. Only correlations with R_A,B > 0.98 are shown. (D) Spider plots indicating the correlated structural communities of PKA-C^F100A and PKA-C^WT plotted on their corresponding structures. The size of each node is independent of the number of residues it encompasses, and the weight of each line indicates the strength of coupling between the individual communities.