Structural Significance of His73 in F-Actin Dynamics: Insights from Ab Initio Study

Figure 1. The atomistic structures of a H-loop on actin in both ATP and ADP states. The corresponding IDs of the PDB sources are 2HF4(ATP) and 2HF3(ADP) [7].

Figure 2. The structural basis for material exchange in F-actin dynamics. The interactions between His73 and Gly158 [8,11] were reported to be important in stabilizing the atomistic networks on actin. The connections between these residues are disrupted during the nucleotide exchange, which helps to create the pathway for material exchange. Once the Pi releases, its mother globular actin would gradually reach the minus end of the actin filament and depolymerize from F-actin.

Figure 3. Conformations of the six His73/Gly158 interactions. The structures of the first three (upper row) are of methyl groups on the side chain. H-bonds (N-H···O) can be found on 1ATN and 2A3Z but not on 1Y64. The binding energies on the unmethylated structures (lower row) are all above zero, which would result in the structural instability of the nucleotide sites on actin. Color key: O, red; C, gray; N, blue; H, silver.

Figure 4. The interaction between His73 and Gly158 could be enhanced by the formation of an H-bond when His73 experiences side chain methylation.

Figure 5. The weak chemical interaction between His73 and Gly158 for both ATP and ADP-actin. The binding energies for ATP-actin are not obligatorily lower than those for ADP-actin. H-bonds (dash circle) could not be found on all ATP-actin structures (PDB codes: 3A5M and 2Hf4), yet it appears in some ADP-actin structures (PDB codes: 1J6Z and 3A5L). The values in the conformation pictures denote the binding energy of the corresponding actin structure. Color key: O, red; C, gray; N, blue; H, silver.