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Tropomyosin is an actin-binding protein that regulates actin mechanics. It is important, among other things, for muscle contraction. Tropomyosin, along with the troponin complex, associate with actin in muscle fibers and regulate muscle contraction by regulating the binding of myosin. In resting muscle, tropomyosin overlays the myosin binding sites on actin, with a single tropomyosin molecule spanning 7 actin subunits, and is "locked" down in this position by troponin T (tropomyosin binding troponin) and troponin I (inhibitory troponin). Upon release of calcium from the sarcoplasmic reticulum calcium binds to troponin C (calcium binding troponin). This "unlocks" tropomyosin from actin, allowing it to move away from the binding groove. Myosin heads can now access the binding sites on actin. Once one myosin head binds, this fully displaces tropomyosin and allows additional myosin heads to bind, initiating muscle shortening and contraction. Once calcium is pumped out of the cytoplasm and calcium levels return to normal, tropomyosin again binds to actin, preventing myosin from binding.
Tropomyosin is an alpha helical coiled coil protein dimer that binds end to end along F actin filaments in striated muscle. Tropomyosin blocks myosin binding and hence crossbridge cycling in the absence of Ca2+. Ca2+ influx from the sarcoplasmic reticulum of striated muscle myocytes binds to troponin and subsequently moves tropomyosin on the F-actin filament, exposing the myosin binding sites.
In this model, tropomyosin can take two conformations: blocked or open. In the blocked state, tropomysoin is locked down to the actin via the troponin complex and myosin is unable to bind actin. Upon release of Ca2+, the troponin complex—specifically troponin C (TnC)—binds calcium, resulting in a conformational change of tropomyosin that physically shifts the protein on actin and fully exposes the myosin binding sites. Myosin can now bind and perform work.
In this model, tropomyosin can take three conformations—blocked, closed, and open. The blocked state is the same as the two-state model. Upon release of Ca2+, however, the troponin complex simply unlocks the tropomyosin from actin, but does not physically move the molecule. The tropomyosin is now free to fluctuate across the actin filament, sometimes blocking it and sometimes exposing it. On average, this can be modeled as a partially blocked myosin binding site and is known as the closed state. If a myosin is able to sneak in and bind actin, it now sterically hinders tropomyosin from covering the myosin binding site, completely exposing this site as well as adjacent myosin binding sites. This is the open state.
Recent structural visualization and kinetic modeling has provided evidence for this model; however, this three-state model is still debated by experts who believe that two-state regulation of muscle contraction (involving a blocked and open state) is sufficient to explain current experimental data and models.
Tropomyosin is a pan-allergen (an allergen widely distributed in nature) because it is a highly conserved protein among species[clarification needed]. Certain tropomyosins are known to cause allergies in certain people, and those who have cross-reactive allergies can get symptoms from a range of sources due to a common allergen found in all these sources: Shrimp, dust mites and mollusks. This common allergen is the reason why some people sensitized with mite tropomyosin could have an allergic reaction after eating seafood.
Tropomyosin is composed of four alpha helices, A, B, C, and D, which coil together to form the quaternary structure.