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TitleRelaxed and active thin filament structures; a new structural basis for the regulatory mechanism.
Journal, issue, pagesJ Struct Biol, Vol. 197, Issue 3, Page 365-371, Year 2017
Publish dateFeb 1, 2017
AuthorsDanielle M Paul / John M Squire / Edward P Morris /
PubMed AbstractThe structures of muscle thin filaments reconstituted using skeletal actin and cardiac troponin and tropomyosin have been determined with and without bound Ca using electron microscopy and reference- ...The structures of muscle thin filaments reconstituted using skeletal actin and cardiac troponin and tropomyosin have been determined with and without bound Ca 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 Ca 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 Ca 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.
External linksJ Struct Biol / PubMed:28161413 / PubMed Central
MethodsEM (single particle)
Resolution27.7 - 28.4 Å
Structure data

3576

5mva

EMDB-3576, PDB-5mva:
Structure of the thin filament at high calcium concentration
Method: EM (single particle) / Resolution: 27.7 Å

3578

5mvy

EMDB-3578, PDB-5mvy:
Thin Filament at low calcium concentration
Method: EM (single particle) / Resolution: 28.4 Å

Chemicals

ChemComp-ADP:
ADENOSINE-5'-DIPHOSPHATE / ADP, energy-carrying molecule*YM / Adenosine diphosphate

Source
  • oryctolagus cuniculus (rabbit)
  • Rabbit (rabbit)
KeywordsSTRUCTURAL PROTEIN / Thin filament / troponin / actin / tropomyosin

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