Fig. 1

Structure of striated tropomyosin and interactions. The tropomyosin molecule (284–285 amino acids) is an α-helical chain that self-assembles into parallel coiled-coil homo or heterodimers. This structure polymerizes head-to-tail to form an uninterrupted coiled-coil along the entire length of actin filaments in both muscle and non-muscle cells. In skeletal muscle, striated isoforms preferentially form heterodimers: Tpm1.1/Tpm2.2 (i.e., αβ dimers) in fast myofibers and Tpm2.2/Tpm3.12 (i.e., γβ dimers) in slow myofibers. The structural organization of tropomyosin is essential for its association with actin filaments, made of weak yet specific electrostatic interactions which enable tropomyosin to shift between regulatory states with a low energy cost. Each striated tropomyosin molecule spans the length of seven consecutive actin monomers. Putative binding regions for actin [14], subunits of the troponin complex [15,16,17], tropomodulin (Tmod) [18], tropomyosin [19], as well as myosin (not shown in the figure) [20], leiomodin (Lmod) (not shown in the figure) [21], and nebulin (not shown in the figure) [22], have been proposed on tropomyosin. N-terminal acetylation (Methionine 1) and C-terminal phosphorylation (serine 284) enhance head-to-tail interaction between neighboring tropomyosin and increase affinity to actin. As we write this review, there exists no atomic resolution of full-length tropomyosin structure. Most studies have used α-chain fragments encoded by the TPM1 gene to decipher the design of the tropomyosin molecule. Furthermore, tropomyosin can adopt different conformations implying binding changes, which have not yet been fully resolved either by crystallography or molecular dynamics (MD) simulation. Despite the high similarity among tropomyosin isoforms, the nature and precise location of putative binding sites on TPM3 isoforms remain in debate