Relaxed and active thin filament structures; a new structural basis for the regulatory mechanism

Danielle Paul, John Squire, Edward Morris

Research output: Contribution to journalArticle (Academic Journal)

14 Citations (Scopus)
251 Downloads (Pure)

Abstract

The structures of muscle thin filaments reconstituted using skeletal actin and cardiac troponin and tropomyosin have been determined with and without bound Ca2+ using electron microscopy and reference-free single particle analysis. The resulting density maps have been fitted with atomic models of actin, tropomyosin and troponin showing that: (i) the polarity of the troponin complex is consistent with our 2009 findings, with large shape changes in troponin between the two states; (ii) without Ca2+ the tropomyosin pseudo-repeats all lie at almost equivalent positions in the ‘blocked’ position on actin (over subdomains 1 and 2); (iii) in the active state the tropomyosin pseudo-repeats are all displaced towards subdomains 3 and 4 of actin, but the extent of displacement varies within the regulatory unit depending upon the axial location of the pseudo-repeats with respect to troponin. Individual pseudo-repeats with Ca2+ bound to troponin can be assigned either to the ‘closed’ state, a partly activated conformation, or the ‘M-state’, a fully activated conformation which has previously been thought to occur only when myosin heads bind. These results lead to a modified view of the steric blocking model of thin filament regulation in which cooperative activation is governed by troponin-mediated local interactions of the pseudo-repeats of tropomyosin with actin.
Original languageEnglish
Pages (from-to)365-371
Number of pages7
JournalJournal of Structural Biology
Volume197
Issue number3
Early online date1 Feb 2017
DOIs
Publication statusPublished - Mar 2017

Keywords

  • Actin
  • Tropomyosin
  • Troponin
  • Thin filament
  • Regulation

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