Cryo-EM structures of the actin: tropomyosin filament reveal the mechanism for the transition from C- to M-State

Duncan Sousa, Scott M. Stagg, M. Elizabeth Stroupe

Research output: Contribution to journalArticle

Abstract

Tropomyosin (Tm) is a key factor in the molecular mechanisms that regulate the binding of myosin motors to actin filaments (F-Actins) in most eukaryotic cells. This regulation is achieved by the azimuthal repositioning of Tm along the actin (Ac):Tm:troponin (Tn) thin filament to block or expose myosin binding sites on Ac. In striated muscle, including involuntary cardiac muscle, Tm regulates muscle contraction by coupling Ca2 + binding to Tn with myosin binding to the thin filament. In smooth muscle, the switch is the posttranslational modification of the myosin. Depending on the activation state of Tn and the binding state of myosin, Tm can occupy the blocked, closed, or open position on Ac. Using native cryogenic 3DEM (three-dimensional electron microscopy), we have directly resolved and visualized cardiac and gizzard muscle Tm on filamentous Ac in the position that corresponds to the closed state. From the 8-Å-resolution structure of the reconstituted Ac:Tm filament formed with gizzard-derived Tm, we discuss two possible mechanisms for the transition from closed to open state and describe the role Tm plays in blocking myosin tight binding in the closed-state position.

Original languageEnglish (US)
Pages (from-to)4544-4555
Number of pages12
JournalJournal of Molecular Biology
Volume425
Issue number22
DOIs
StatePublished - Nov 15 2013
Externally publishedYes

Fingerprint

Tropomyosin
Actin Cytoskeleton
Myosins
Actins
Troponin
Smooth Muscle
Myocardium
Striated Muscle
Eukaryotic Cells
Post Translational Protein Processing
Muscle Contraction
Electron Microscopy
Binding Sites

Keywords

  • actin
  • cryogenic 3DEM
  • cytoskeleton
  • thin filament
  • tropomyosin

ASJC Scopus subject areas

  • Molecular Biology

Cite this

Cryo-EM structures of the actin : tropomyosin filament reveal the mechanism for the transition from C- to M-State. / Sousa, Duncan; Stagg, Scott M.; Stroupe, M. Elizabeth.

In: Journal of Molecular Biology, Vol. 425, No. 22, 15.11.2013, p. 4544-4555.

Research output: Contribution to journalArticle

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