Tropomyosin

Tropomyosin is a long, rod-shaped coiled-coil protein that binds along actin filaments in muscle and non-muscle cells. It stabilizes actin filaments and plays a central role in regulating actin–myosin interactions during contraction.

In vertebrates, tropomyosin exists as multiple isoforms encoded by four genes (TPM1, TPM2, TPM3, TPM4) that yield various protein variants. The canonical skeletal muscle isoform is alpha-tropomyosin (TPM1); beta-tropomyosin (TPM2) is abundant in smooth muscle and brain. Tropomyosin dimers form parallel coiled coils about 40 nanometers long that align along the groove of actin filaments.

In skeletal (striated) muscle, tropomyosin works with the troponin complex (troponin I, C, and T) to regulate myosin binding to actin. At rest, tropomyosin blocks myosin-binding sites on actin. When intracellular Ca2+ rises, Ca2+ binds to troponin C, inducing a shift that moves tropomyosin away from these sites, exposing them for myosin engagement and enabling contraction.

In smooth muscle and in non-muscle cells, regulation is different. Smooth muscle contraction primarily involves phosphorylation of myosin light chains by myosin light chain kinase to permit actin–myosin interaction, with tropomyosin contributing to filament stability and localization and interacting with other actin-binding proteins such as caldesmon. Non-muscle tropomyosin isoforms help organize and stabilize actin networks in the cytoskeleton.

Mutations in TPM1–TPM4 genes are associated with inherited muscle diseases and cardiomyopathies; TPM2 and TPM3 mutations have been linked to distal arthrogryposis, nemaline myopathy, and related conditions. Tropomyosin is also a common allergen in shellfish and other invertebrates, capable of triggering IgE-mediated reactions in sensitized individuals.