Tropomyosin conformation

When the sarcolemma is excited by a nerve impulse, the signal is transmitted into the T tubule system and a release channel in the nearby sarcoplasmic reticulum opens, releasing Ca + from the sarcoplasmic reticulum into the sarcoplasm. The concentration of Ca in the sarcoplasm rises rapidly to 10 mol/L. The Ca -binding sites on TpC in the thin filament are quickly occupied by Ca +. The TpC-4Ca + interacts with Tpl and TpT to alter their interaction with tropomyosin. Accordingly, tropomyosin moves out of the way or alters the conformation of F-actin so that the myosin head-ADP-P (Figure 49-6) can interact with F-actin to start the contraction cycle. 

Calcium binds to troponin C on tropomyosin, causing a conformational change that exposes myosin-binding sites on actin. 

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.

It is troponin that responds to the increased Ca centration. The Ca ions bind to Tn-C, which then binds to Tn-I and causes a conformational change in Tn-T. This results in a conformational change in tropomyosin that exposes sites on the actin filament for binding with the myosin head of the cross-bridge. The process can be summarised as follows (see also Figure 13.16) ... 

A nerve impulse causes release of Ca2+ from the sarcoplasmic reticulum. The released Ca2+ binds to troponin (another protein-ligand interaction) and causes a conformational change in the tropomyosin-troponin complexes, exposing the myosin-binding sites on the thin filaments. Contraction follows. 

The Ca2+ binds to the protein troponin, leading to a conformational change in a troponin-tropomyosin complex that triggers the cycle of actin-myosin interactions. 

Troponin s role in the thin filament of vertebrate striated muscles is primarily that of regulation. The three subunits of this complex form what has been described as a Ca2+-sensitive latch that fixes tropomyosin s position on the actin helix in the off state of contraction (Lehman et al., 2001). One subunit of the complex, troponin T (TnT), maintains an invariant linkage to tropomyosin, and another, troponin I (Tnl), a variable linkage to actin. The third subunit, troponin (TnC) is the Ca2+sensor of the complex and indeed of the myofibril itself. The latch is opened or closed depending on the level of Ca2+. Correspondingly, a series of conformational changes takes place in the entire complex and in the thin... 

Repeating surface residues of tropomyosin appear to interact direcdy with recognition sites on consecutive monomers of F-actin. We first discuss, however, the repeat in the core, which, although less regular than that of certain surface residues (see below), has a clearly understood effect on the conformational and dynamic properties of the coiled-coil. 

Tropomyosin is an elongated protein that lies along the thin filament and prevents the association of myosin with actin in the resting state. Troponin is a complex of three polypeptide chains TnC, Tnl and TnT. Ca2+ ions released into the sarcoplasm from the sarcoplasmic reticulum in response to a nerve stimulation bind to TnC and cause a conformational change in the protein. This movement is transmitted by an allosteric mechanism through Tnl and TnT to tropomyosin, causing the latter to move out of the way and allowing the actin and myosin to associate. 

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