Structural basis for the regulation of muscle contraction by troponin and tropomyosin
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Authors
Galinska-Rakoczy, AgnieszkaEngel, Patti
Xu, Chen
Jung, HyunSuk
Craig, Roger W.
Tobacman, Larry S.
Lehman, William
UMass Chan Affiliations
Department of Cell BiologyDocument Type
Journal ArticlePublication Date
2008-06-03Keywords
ActinsHumans
Image Processing, Computer-Assisted
Microscopy, Electron, Transmission
Models, Biological
Models, Molecular
Multiprotein Complexes
Muscle Contraction
Protein Engineering
Protein Structure, Quaternary
Recombinant Proteins
Tropomyosin
Troponin
Troponin I
Cell Biology
Metadata
Show full item recordAbstract
The molecular switching mechanism governing skeletal and cardiac muscle contraction couples the binding of Ca2+ on troponin to the movement of tropomyosin on actin filaments. Despite years of investigation, this mechanism remains unclear because it has not yet been possible to directly assess the structural influence of troponin on tropomyosin that causes actin filaments, and hence myosin-crossbridge cycling and contraction, to switch on and off. A C-terminal domain of troponin I is thought to be intimately involved in inducing tropomyosin movement to an inhibitory position that blocks myosin-crossbridge interaction. Release of this regulatory, latching domain from actin after Ca2+ binding to TnC (the Ca2+ sensor of troponin that relieves inhibition) presumably allows tropomyosin movement away from the inhibitory position on actin, thus initiating contraction. However, the structural interactions of the regulatory domain of TnI (the "inhibitory" subunit of troponin) with tropomyosin and actin that cause tropomyosin movement are unknown, and thus, the regulatory process is not well defined. Here, thin filaments were labeled with an engineered construct representing C-terminal TnI, and then, 3D electron microscopy was used to resolve where troponin is anchored on actin-tropomyosin. Electron microscopy reconstruction showed how TnI binding to both actin and tropomyosin at low Ca2+ competes with tropomyosin for a common site on actin and drives tropomyosin movement to a constrained, relaxing position to inhibit myosin-crossbridge association. Thus, the observations reported reveal the structural mechanism responsible for troponin-tropomyosin-mediated steric interference of actin-myosin interaction that regulates muscle contraction.Source
J Mol Biol. 2008 Jun 20;379(5):929-35. Epub 2008 May 3. Link to article on publisher's siteDOI
10.1016/j.jmb.2008.04.062Permanent Link to this Item
http://hdl.handle.net/20.500.14038/27684PubMed ID
18514658Related Resources
Link to Article in PubMedae974a485f413a2113503eed53cd6c53
10.1016/j.jmb.2008.04.062