Structural basis for the activation of muscle contraction by troponin and tropomyosin
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UMass Chan Affiliations
Department of Cell BiologyDocument Type
Journal ArticlePublication Date
2009-04-04Keywords
CalciumMicrofilaments
Models, Molecular
Muscle Contraction
*Muscles
*Protein Conformation
Surface Properties
*Tropomyosin
*Troponin I
*Troponin T
Amino Acids, Peptides, and Proteins
Cell Biology
Investigative Techniques
Macromolecular Substances
Musculoskeletal, Neural, and Ocular Physiology
Metadata
Show full item recordAbstract
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.Source
J Mol Biol. 2009 May 15;388(4):673-81. Epub 2009 Mar 31. Link to article on publisher's site
DOI
10.1016/j.jmb.2009.03.060Permanent Link to this Item
http://hdl.handle.net/20.500.14038/27678PubMed ID
19341744Related Resources
ae974a485f413a2113503eed53cd6c53
10.1016/j.jmb.2009.03.060