tropomiozin

Tropomiozin is a long, rod-shaped protein that binds along actin filaments as a parallel coiled-coil dimer. Each subunit is about 284 amino acids, yielding roughly 32 kilodaltons, and two subunits form a dimer that polymerizes head-to-tail to cover a length of actin along the filament. It is encoded by TPM1, TPM2, TPM3 and TPM4, with multiple tissue-specific isoforms produced by alternative splicing. Tropomiozin is a major component of the actin thin filament in most eukaryotic cells and exists in both muscle and non-muscle forms.

In striated muscle, tropomiozin works with the troponin complex to regulate contraction. In resting muscle, tropomiozin blocks myosin-binding sites on actin. Upon calcium binding to troponin C, the troponin complex shifts tropomiozin away, exposing the sites and allowing myosin cross-bridge cycling. In smooth muscle, regulation involves calcium-activated calmodulin and myosin light chain kinase, with tropomiozin interacting with other regulatory proteins such as caldesmon and calponin; in both cases, tropomiozin contributes to the control of filament interaction rather than serving as the sole switch.

Non-muscle tropomiozin isoforms stabilize actin networks, organize cytoskeleton architecture, and influence cell migration, adhesion, and division. The TPM genes show broad expression, with tissue-specific isoforms that confer functional differences in filament stability and interactions with actin-binding proteins.

Clinical relevance: Mutations and variants in TPM genes are linked to inherited cardiomyopathies (notably dilated cardiomyopathy) and skeletal muscle disorders such as distal arthrogryposis and congenital myopathies. Tropomiozin’s essential role in cytoskeletal integrity accounts for the severity of disruptions in muscle performance. Tropomiozin is highly conserved across eukaryotes and is a hallmark of the actin cytoskeleton.