Role of Hsp70 ATPase Domain Intrinsic Dynamics and Sequence Evolution in Enabling its Functional Interactions with NEFs
Figure 6
Co-evolution of NEF-binding residues revealed by mutual information (MI) maps constructed for the Hsp70 ATPase domain.
(a) Amino acids distinguished by their high co-evolutionary patterns in the maps c and d (residues with average MI value greater than 0.32), shown in stick representation and colored by subdomains. Among them, the NEF contacting residues (Table S1) are labeled black, and others are colored by subdomain. Note the large proportion of charged or polar residues. (b) MI map for the ATPase domain sequence included in the MSA (residues 6–385). The color-coded bar on the right indicates the level of correlation between the evolution of residue pairs. Two regions containing a large number of NEF-binding residues are enlarged in panels c and d. The bar plots under the map display the contribution of each residue to the most correlated residue pairs (top 1%, 720 pairs) in the MI matrix (upper plot), and the frequency of NEF-ATPase domain contacts in three mammalian complexes (lower plot). (c) and (d) Close-up views of the MI map portions between residues 246–305 (containing the helix 9 and β-sheet E of subdomain IIB) and residues 16–75 (containing NEF-contacting segments in subdomains IA and IB) (c), and within residues 246–305 (d). The corresponding secondary structural elements are indicated along the abscissa by cylinders (α-helices) and arrows (β-strands). The bar plots display the average MI per residue, NEF binding residues being colored by their subdomain.