Tropomyosin actin binding

Miki M, Dosremedios CG (1988) Fluorescence quenching studies of fluorescein attached to Lys-61 or Cys-374 in actin effects of polymerization, myosin subfragment-1 binding, and tropomyosin-troponin binding. J Biochem Tokyo 104 232-235... 

Figure 13.7 A diagram of the actin helix showing position of the tropomyosin. Both actin chains are flanked by tropomyosin molecules, which are long string-like molecules that span seven actin monomers. The troponin complex is attached to the tropomyosin but is not shown. From this diagram, it should be clear how the tropomyosin molecule can conceal the actin-binding sites for the myosin cross-bridges in the relaxed condition. A small conformational change in tropomyosin exposes the sites for attachment of the cross-bridges.

The regulatory proteins troponin and tropomyosin 1118 Table 19-1 Some Actin-Binding Proteins... 

Stewart, M., and McLachlan, A. D. (1975). Fourteen actin-binding sites on tropomyosin Nature 257, 331—333. 

Sano, K.-I., Maeda, K., Oda, T., and Maeda, Y. (2000). The effect of single residue substitutions of serine-283 on the strength of head-to-tail interaction and actin binding properties of rabbit skeletal muscle a-tropomyosin. /. Biochem. 127, 1095-1102. 

Singh, A., and Hitchcock-DeGregori, S. E. (2003). Local destabilization of the tropomyosin coiled-coil gives the molecular flexibility required for actin binding. Biochemistry 42, 14114-14121. 

Smillie, L.B., Pato, M.D., Pearlstone, J.R., Mak, A.S. 1980. Periodicity of alpha-helical potential in tropomyosin sequence correlates with alternating actin binding-sites. Journal of Molecular Biology 136(2) 199-202. 

Figure 6.3. Stractuie and function of myofilaments, a Arrangement of proteins within the filaments, b, c Mechanism of myofilament motion. Calcium binds to troponin, which in tnm causes tropomyosin to move and expose the myosin binding site on actin. Binding to actin canses the myosin heads to kink, which translates into a sliding motion, c The kinked conformation of myosin cleaves ATP. In the process, myosin releases itself from actin and letnms to the extended conformation it then binds to another actin monomer, and the cycle is repeated.

Paratropomyosin (34 kDa x 2), discovered by Takahashi etal. (1985), is a protein very similar to tropomyosin, but is located at the A-I junction region and translocated to the I-band region to release myosin and actin binding in postmortem myofibrils. 

Under certain experimental conditions, tropomyosin inhibits actomy-osin ATPase activity by binding to actin. This inhibition is potentiated by troponin I with some increase in the binding of tropomyosin to actin (Eaton et al., 1975). Troponin I may connect tropomyosin and actin, or it may induce tropomyosin to bind to actin. 

The strong binding of the troponin T i region to tropomyosin should undoubtedly contribute to the steric stabilization of the position of the whole troponin complex on tropomyosin—actin. The Ca + sensitivity of actomyosin ATPase by troponin T2 is a little less cooperative than that by troponin T, and thus the depressive effect of free Mg " on the Ca sensitivity of the actomyosin ATPase with troponin T2 is less remarkable. Troponin T1 may be involved in these aspects. The maximum activation of actomyosin ATPase by troponin T2 in the presence of tropomyosin-troponin I-C was a litde less than that by troponin T. Troponin Ti itself depressed the ATPase and superprecipitation of actomyosin-tropomyo-sin-troponin I-C at all Ca + concentrations. The mixture of troponin Ti and T2 also depressed the ATPase at all Ca concentrations to the same extent as troponin Ti. This suggests that the native position of troponin Ti in the thin filament is different from that of isolated troponin T1 in the reconstituted filament. 

In the absence of troponin I inhibits the thin filament from interacting with myosin. Troponin T is also involved in this inhibition. Troponin T, on one hand, binds to tropomyosin and, on the other hand, binds to troponin I. The action of troponin T is mosdy to adjust the relation of troponin I to tropomyosin—actin for the inhibitory state in the absence of Ca. ... 

Both smooth and skeletal muscle actin filaments are saturated with tropomyosin (Sobieszek and Bremel 1975). Both exhibit the same characteristic stoichiometry of binding of 1 molecule of tropomyosin interacting with 7 monomeric units of F-actin on each of the two strands of F-actin (Hartshorne 1987). The length of tropomyosin molecules (284 amino acids) and their periodicity in smooth and striated muscles is the same (Matsumura and Lin 1982). In both tissues, tropomyosin exists as a dimeric a-helical coil (Caspar et al 1969). Individual tropomyosin molecules bind in an end to end fashion to form a continuous strand on the thin filament that lies along the long-pitch of the double helix formed by the actin monomers (Moore et al 1970, OBrien et al 1971, Spudich et al 1972, Milligan et al 1990). 

The distribution of actin and tropomyosin are generally agreed to be highly correlated throughout the cytoplasm, and in native thin filaments, tropomyosin appears to be bound to all actin filament isoforms (Mabuchi et al 1996, Small et al 1986). However, there is evidence from a number of laboratories that different actin-binding proteins associate selectively with different actin isoforms and localize to different functional domains within smooth muscle cells. 

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