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dc.contributor.authorLehman, William
dc.contributor.authorGalinska-Rakoczy, Agnieszka
dc.contributor.authorHatch, Victoria
dc.contributor.authorTobacman, Larry S.
dc.contributor.authorCraig, Roger W.
dc.date2022-08-11T08:08:12.000
dc.date.accessioned2022-08-23T15:46:05Z
dc.date.available2022-08-23T15:46:05Z
dc.date.issued2009-04-04
dc.date.submitted2010-10-06
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.issn0022-2836 (Linking)
dc.identifier.doi10.1016/j.jmb.2009.03.060
dc.identifier.pmid19341744
dc.identifier.urihttp://hdl.handle.net/20.500.14038/27678
dc.description.abstractThe 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.isoen_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.urlhttp://www.ncbi.nlm.nih.gov/pmc/articles/PMC2693027
dc.subjectCalcium
dc.subjectMicrofilaments
dc.subjectModels, Molecular
dc.subjectMuscle Contraction
dc.subject*Muscles
dc.subject*Protein Conformation
dc.subjectSurface Properties
dc.subject*Tropomyosin
dc.subject*Troponin I
dc.subject*Troponin T
dc.subjectAmino Acids, Peptides, and Proteins
dc.subjectCell Biology
dc.subjectInvestigative Techniques
dc.subjectMacromolecular Substances
dc.subjectMusculoskeletal, Neural, and Ocular Physiology
dc.titleStructural basis for the activation of muscle contraction by troponin and tropomyosin
dc.typeJournal Article
dc.source.journaltitleJournal of molecular biology
dc.source.volume388
dc.source.issue4
dc.identifier.legacycoverpagehttps://escholarship.umassmed.edu/craig/3
dc.identifier.contextkey1594902
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.submissionpathcraig/3
dc.contributor.departmentDepartment of Cell Biology
dc.source.pages673-81


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