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7687427 
Journal Article 
Structural basis for the activation of muscle contraction by troponin and tropomyosin 
Lehman, W; Galińska-Rakoczy, A; Hatch, V; Tobacman, LS; Craig, R; , 
2009 
Yes 
Journal of Molecular Biology
ISSN: 0022-2836
EISSN: 1089-8638 
ACADEMIC PRESS LTD- ELSEVIER SCIENCE LTD 
LONDON 
388 
4 
673-681 
English 
19341744 
WOS:000266302500001 
The molecular regulation of striated muscle contraction couples the binding and dissociation of Ca(2+) on troponin (Tn) to the movement of tropomyosin on actin filaments. In turn, this process exposes or blocks myosin binding sites on actin, thereby controlling myosin crossbridge dynamics and consequently muscle contraction. Using 3D electron microscopy, we recently provided structural evidence that a C-terminal extension of TnI is anchored on actin at low Ca(2+) and competes with tropomyosin for a common site to drive tropomyosin to the B-state location, a constrained, relaxing position on actin that inhibits myosin-crossbridge association. Here, we show that release of this constraint at high Ca(2+) allows a second segment of troponin, probably representing parts of TnT or the troponin core domain, to promote tropomyosin movement on actin to the Ca(2+)-induced C-state location. With tropomyosin stabilized in this position, myosin binding interactions can begin. Tropomyosin appears to oscillate to a higher degree between respective B- and C-state positions on troponin-free filaments than on fully regulated filaments, suggesting that tropomyosin positioning in both states is troponin-dependent. By biasing tropomyosin to either of these two positions, troponin appears to have two distinct structural functions; in relaxed muscles at low Ca(2+), troponin operates as an inhibitor, while in activated muscles at high Ca(2+), it acts as a promoter to initiate contraction. 
actin; calcium; electron microscopy; tropomyosin; troponin