Abstract
Formins catalyze the nucleation and growth of actin filaments. Here we study both the structure and interactions of actin with the FH2 domain of budding yeast formin Bni1p. We built an all-atom model of the formin dimer on an Oda actin filament 7-mer and studied structural relaxation and interactions between formin and actin by molecular dynamics simulations. These simulations produced a refined model for the FH2 dimer associated with the barbed end of the actin filament and revealed the presence of electrostatic interactions between the formin knob and actin target-binding cleft. Mutations of two formin residues which contribute to these interactions (R1423N, K1467L or both) reduced the interaction energies between the proteins, and in coarse-grained simulations the formin lost more inter-protein contacts with an actin dimer than with an actin 7-mer. Biochemical experiments confirmed that there is a strong influence of these mutations on Bni1p-mediated actin filament nucleation, but not elongation. This suggests that there are different interactions that contribute to these two functions of formins.
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