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dc.contributor.authorWoodhead, John L.
dc.contributor.authorZhao, Fa-Qing
dc.contributor.authorCraig, Roger W.
dc.date2022-08-11T08:08:34.000
dc.date.accessioned2022-08-23T15:59:15Z
dc.date.available2022-08-23T15:59:15Z
dc.date.issued2013-05-21
dc.date.submitted2013-06-05
dc.identifier.citationProc Natl Acad Sci U S A. 2013 May 21;110(21):8561-6. doi: 10.1073/pnas.1218462110. <a href="http://dx.doi.org/10.1073/pnas.1218462110">Link to article on publisher's site</a>
dc.identifier.issn0027-8424 (Linking)
dc.identifier.doi10.1073/pnas.1218462110
dc.identifier.pmid23650385
dc.identifier.urihttp://hdl.handle.net/20.500.14038/30622
dc.description.abstractMyosin filaments of muscle are regulated either by phosphorylation of their regulatory light chains or Ca(2+) binding to the essential light chains, contributing to on-off switching or modulation of contraction. Phosphorylation-regulated filaments in the relaxed state are characterized by an asymmetric interaction between the two myosin heads, inhibiting their actin binding or ATPase activity. Here, we have tested whether a similar interaction switches off activity in myosin filaments regulated by Ca(2+) binding. Cryo-electron microscopy and single-particle image reconstruction of Ca(2+)-regulated (scallop) filaments reveals a helical array of myosin head-pair motifs above the filament surface. Docking of atomic models of scallop myosin head domains into the motifs reveals that the heads interact in a similar way to those in phosphorylation-regulated filaments. The results imply that the two major evolutionary branches of myosin regulation-involving phosphorylation or Ca(2+) binding-share a common structural mechanism for switching off thick-filament activity in relaxed muscle. We suggest that the Ca(2+)-binding mechanism evolved from the more ancient phosphorylation-based system to enable rapid response of myosin-regulated muscles to activation. Although the motifs are similar in both systems, the scallop structure is more tilted and higher above the filament backbone, leading to different intermolecular interactions. The reconstruction reveals how the myosin tail emerges from the motif, connecting the heads to the filament backbone, and shows that the backbone is built from supramolecular assemblies of myosin tails. The reconstruction provides a native structural context for understanding past biochemical and biophysical studies of this model Ca(2+)-regulated myosin.
dc.language.isoen_US
dc.relation<a href="http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?db=pubmed&cmd=Retrieve&list_uids=23650385&dopt=Abstract">Link to Article in PubMed</a>
dc.relation.urlhttp://dx.doi.org/10.1073/pnas.1218462110
dc.subjectCalcium-Binding Proteins
dc.subjectMyosins
dc.subjectCell and Developmental Biology
dc.subjectCell Biology
dc.titleStructural basis of the relaxed state of a Ca2+-regulated myosin filament and its evolutionary implications
dc.typeJournal Article
dc.source.journaltitleProceedings of the National Academy of Sciences of the United States of America
dc.source.volume110
dc.source.issue21
dc.identifier.legacycoverpagehttps://escholarship.umassmed.edu/faculty_pubs/9
dc.identifier.contextkey4199939
html.description.abstract<p>Myosin filaments of muscle are regulated either by phosphorylation of their regulatory light chains or Ca(2+) binding to the essential light chains, contributing to on-off switching or modulation of contraction. Phosphorylation-regulated filaments in the relaxed state are characterized by an asymmetric interaction between the two myosin heads, inhibiting their actin binding or ATPase activity. Here, we have tested whether a similar interaction switches off activity in myosin filaments regulated by Ca(2+) binding. Cryo-electron microscopy and single-particle image reconstruction of Ca(2+)-regulated (scallop) filaments reveals a helical array of myosin head-pair motifs above the filament surface. Docking of atomic models of scallop myosin head domains into the motifs reveals that the heads interact in a similar way to those in phosphorylation-regulated filaments. The results imply that the two major evolutionary branches of myosin regulation-involving phosphorylation or Ca(2+) binding-share a common structural mechanism for switching off thick-filament activity in relaxed muscle. We suggest that the Ca(2+)-binding mechanism evolved from the more ancient phosphorylation-based system to enable rapid response of myosin-regulated muscles to activation. Although the motifs are similar in both systems, the scallop structure is more tilted and higher above the filament backbone, leading to different intermolecular interactions. The reconstruction reveals how the myosin tail emerges from the motif, connecting the heads to the filament backbone, and shows that the backbone is built from supramolecular assemblies of myosin tails. The reconstruction provides a native structural context for understanding past biochemical and biophysical studies of this model Ca(2+)-regulated myosin.</p>
dc.identifier.submissionpathfaculty_pubs/9
dc.contributor.departmentDepartment of Cell and Development Biology
dc.source.pages8561-6


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