The Three-Dimensional Model of the Tropomodulin Assembly at the Pointed End of Actin Filament

Actin filaments have the pointed (slow growing) end and barbed (fast end. Interactions with actin-binding proteins at each enable control of length actin filaments. Tropomodulin (Tmod) modulates filament by interacting tropomyosin (Tpm) filament. Tmod binds two Tpm molecules through distinct binding sites – site 1 2. Establishing structure Tmod-Tpm interface is critical to understand mechanism regulation dynamics Tmod. In this study, we built three-dimensional models complexes using (1) structural information obtained from NMR data for fragments representing sites, (2) secondary predictions. To refine models, employed simulated annealing molecular followed conventional simulations. The refined modeled structures reveal similarities between Tmod2s1 Tmod2s2 (representing 2, respectively) fragment. both complexes, form an α-helical hairpin arranged coiled coil in a four-α-helix bundle. Positioning over N-terminus blocks further polymerization prevents elongation cable. Both are stabilized hydrophobic core formed residues that conserved sites. known were used dock associated cables. model pointed-end assembly offers new insights into how ensures tight dynamics.