Structural basis for the activation of muscle contraction by troponin and tropomyosin
dc.contributor.author | Lehman, William | |
dc.contributor.author | Galinska-Rakoczy, Agnieszka | |
dc.contributor.author | Hatch, Victoria | |
dc.contributor.author | Tobacman, Larry S. | |
dc.contributor.author | Craig, Roger W. | |
dc.date | 2022-08-11T08:08:12.000 | |
dc.date.accessioned | 2022-08-23T15:46:05Z | |
dc.date.available | 2022-08-23T15:46:05Z | |
dc.date.issued | 2009-04-04 | |
dc.date.submitted | 2010-10-06 | |
dc.identifier.citation | <p>J Mol Biol. 2009 May 15;388(4):673-81. Epub 2009 Mar 31. <a href="http://dx.doi.org/10.1016/j.jmb.2009.03.060">Link to article on publisher's site</a></p> | |
dc.identifier.issn | 0022-2836 (Linking) | |
dc.identifier.doi | 10.1016/j.jmb.2009.03.060 | |
dc.identifier.pmid | 19341744 | |
dc.identifier.uri | http://hdl.handle.net/20.500.14038/27678 | |
dc.description.abstract | 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. | |
dc.language.iso | en_US | |
dc.relation | <p><a href="http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?db=pubmed&cmd=Retrieve&list_uids=19341744&dopt=Abstract">Link to Article in PubMed</a></p> | |
dc.relation.url | http://www.ncbi.nlm.nih.gov/pmc/articles/PMC2693027 | |
dc.subject | Calcium | |
dc.subject | Microfilaments | |
dc.subject | Models, Molecular | |
dc.subject | Muscle Contraction | |
dc.subject | *Muscles | |
dc.subject | *Protein Conformation | |
dc.subject | Surface Properties | |
dc.subject | *Tropomyosin | |
dc.subject | *Troponin I | |
dc.subject | *Troponin T | |
dc.subject | Amino Acids, Peptides, and Proteins | |
dc.subject | Cell Biology | |
dc.subject | Investigative Techniques | |
dc.subject | Macromolecular Substances | |
dc.subject | Musculoskeletal, Neural, and Ocular Physiology | |
dc.title | Structural basis for the activation of muscle contraction by troponin and tropomyosin | |
dc.type | Journal Article | |
dc.source.journaltitle | Journal of molecular biology | |
dc.source.volume | 388 | |
dc.source.issue | 4 | |
dc.identifier.legacycoverpage | https://escholarship.umassmed.edu/craig/3 | |
dc.identifier.contextkey | 1594902 | |
html.description.abstract | <p>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.</p> | |
dc.identifier.submissionpath | craig/3 | |
dc.contributor.department | Department of Cell Biology | |
dc.source.pages | 673-81 |
Files in this item
This item appears in the following Collection(s)
-
Padrón-Craig Lab [74]