TropomyosinTroponin

Tropomyosin and troponin are regulatory proteins that control muscle contraction in striated muscle, functioning together on the thin filament of the sarcomere. Tropomyosin is a rod-shaped, alpha-helical protein that forms a coiled-coil dimer, running along the groove of actin filaments. Troponin is a calcium-binding, regulatory complex that associates with tropomyosin at regular intervals on actin. The combined tropomyosin–troponin complex acts as a molecular switch that governs access to the myosin-binding sites on actin, thereby modulating contraction in skeletal and cardiac muscle.

Tropomyosin binds along actin filaments and stabilizes the thin filament structure. It blocks myosin-binding sites on actin at rest, preventing cross-bridge formation. The protein exists in multiple isoforms produced by TPM gene family members, including TPM1, TPM2, TPM3, and TPM4, with tissue- and development-specific expression that influences filament regulation and mechanical properties.

Troponin is a heterotrimer composed of three subunits: troponin C (TNNC), which binds calcium ions; troponin I (TNNI), which inhibits actin–myosin interaction; and troponin T (TNNT), which anchors the complex to tropomyosin. In humans, there are distinct cardiac and skeletal muscle isoforms (for example, TNNC1/TNNC2, TNNI3/TNNI1/TNNI2, TNNT2/TNNT1/TNNT3), allowing tissue-specific regulation of contraction.

Mechanism of regulation involves calcium-dependent conformational changes. In the absence of calcium, tropomyosin obstructs myosin-binding sites on actin. When intracellular calcium rises, calcium binds TNNC, triggering a shift of the troponin–tropomyosin complex that exposes the sites for cross-bridge cycling and muscle contraction.

Clinically, troponin I and troponin T are widely used as biomarkers of myocardial injury. Genetic mutations in troponin or tropomyosin genes can cause inherited cardiomyopathies and skeletal myopathies, reflecting their critical roles in muscle contractility.