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dc.contributor.authorPirani, Alnoor
dc.contributor.authorXu, Chen
dc.contributor.authorHatch, Victoria
dc.contributor.authorCraig, Roger W.
dc.contributor.authorTobacman, Larry S.
dc.contributor.authorLehman, William
dc.date2022-08-11T08:08:12.000
dc.date.accessioned2022-08-23T15:46:01Z
dc.date.available2022-08-23T15:46:01Z
dc.date.issued2005-02-17
dc.date.submitted2010-10-06
dc.identifier.citationJ Mol Biol. 2005 Feb 25;346(3):761-72. Epub 2005 Jan 11. <a href="http://dx.doi.org/10.1016/j.jmb.2004.12.013">Link to article on publisher's site</a>
dc.identifier.issn0022-2836 (Linking)
dc.identifier.doi10.1016/j.jmb.2004.12.013
dc.identifier.pmid15713461
dc.identifier.urihttp://hdl.handle.net/20.500.14038/27664
dc.description.abstractThe movement of tropomyosin from actin's outer to its inner domain plays a key role in sterically regulating muscle contraction. This movement, from a low Ca2+ to a Ca2+-induced position has been directly demonstrated by electron microscopy and helical reconstruction. Solution studies, however, suggest that tropomyosin oscillates dynamically between these positions at all Ca2+ levels, and that it is the position of this equilibrium that is controlled by Ca2+. Helical reconstruction reveals only the average position of tropomyosin on the filament, and not information on the local dynamics of tropomyosin in any one Ca2+ state. We have therefore used single particle analysis to analyze short filament segments to reveal local variations in tropomyosin behavior. Segments of Ca2+-free and Ca2+ treated thin filaments were sorted by cross-correlation to low and high Ca2+ models of the thin filament. Most segments from each data set produced reconstructions matching those previously obtained by helical reconstruction, showing low and high Ca2+ tropomyosin positions for low and high Ca2+ filaments. However, approximately 20% of segments from Ca2+-free filaments fitted best to the high Ca2+ model, yielding a corresponding high Ca2+ reconstruction. Conversely, approximately 20% of segments from Ca2+-treated filaments fitted best to the low Ca2+ model and produced a low Ca2+ reconstruction. Hence, tropomyosin position on actin is not fixed in either Ca2+ state. These findings provide direct structural evidence for the equilibration of tropomyosin position in both high and low Ca2+ states, and for the concept that Ca2+ controls the position of this equilibrium. This flexibility in the localization of tropomyosin may provide a means of sterically regulating contraction at low energy cost.
dc.language.isoen_US
dc.relation<a href="http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?db=pubmed&cmd=Retrieve&list_uids=15713461&dopt=Abstract">Link to Article in PubMed</a>
dc.relation.urlhttp://dx.doi.org/10.1016/j.jmb.2004.12.013
dc.subjectActins
dc.subjectAnimals
dc.subjectBinding Sites
dc.subjectCalcium
dc.subjectCattle
dc.subjectImage Processing, Computer-Assisted
dc.subjectMicroscopy, Electron
dc.subjectModels, Molecular
dc.subjectMultiprotein Complexes
dc.subjectMuscle Contraction
dc.subjectMuscle Proteins
dc.subjectMuscle Relaxation
dc.subjectMuscle, Skeletal
dc.subjectMyocardial Contraction
dc.subjectMyocardium
dc.subjectRabbits
dc.subjectTropomyosin
dc.subjectTroponin
dc.subjectCell Biology
dc.titleSingle particle analysis of relaxed and activated muscle thin filaments
dc.typeJournal Article
dc.source.journaltitleJournal of molecular biology
dc.source.volume346
dc.source.issue3
dc.identifier.legacycoverpagehttps://escholarship.umassmed.edu/craig/17
dc.identifier.contextkey1594916
html.description.abstract<p>The movement of tropomyosin from actin's outer to its inner domain plays a key role in sterically regulating muscle contraction. This movement, from a low Ca2+ to a Ca2+-induced position has been directly demonstrated by electron microscopy and helical reconstruction. Solution studies, however, suggest that tropomyosin oscillates dynamically between these positions at all Ca2+ levels, and that it is the position of this equilibrium that is controlled by Ca2+. Helical reconstruction reveals only the average position of tropomyosin on the filament, and not information on the local dynamics of tropomyosin in any one Ca2+ state. We have therefore used single particle analysis to analyze short filament segments to reveal local variations in tropomyosin behavior. Segments of Ca2+-free and Ca2+ treated thin filaments were sorted by cross-correlation to low and high Ca2+ models of the thin filament. Most segments from each data set produced reconstructions matching those previously obtained by helical reconstruction, showing low and high Ca2+ tropomyosin positions for low and high Ca2+ filaments. However, approximately 20% of segments from Ca2+-free filaments fitted best to the high Ca2+ model, yielding a corresponding high Ca2+ reconstruction. Conversely, approximately 20% of segments from Ca2+-treated filaments fitted best to the low Ca2+ model and produced a low Ca2+ reconstruction. Hence, tropomyosin position on actin is not fixed in either Ca2+ state. These findings provide direct structural evidence for the equilibration of tropomyosin position in both high and low Ca2+ states, and for the concept that Ca2+ controls the position of this equilibrium. This flexibility in the localization of tropomyosin may provide a means of sterically regulating contraction at low energy cost.</p>
dc.identifier.submissionpathcraig/17
dc.contributor.departmentDepartment of Cell Biology
dc.source.pages761-72


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