Topology of interaction between titin and myosin thick filaments

M. Kellermayer, Dominik Sziklai, Zsombor Papp, Brennan Decker, Eszter Lakatos, Zsolt Mártonfalvi

Research output: Contribution to journalArticle

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Abstract

Titin is a giant protein spanning between the Z- and M-lines of the sarcomere. In the A-band titin is associated with the myosin thick filament. It has been speculated that titin may serve as a blueprint for thick-filament formation due to the super-repeat structure of its A-band domains. Accordingly, titin might provide a template that determines the length and structural periodicity of the thick filament. Here we tested the titin ruler hypothesis by mixing titin and myosin at in situ stoichiometric ratios (300 myosins per 12 titins) in buffers of different ionic strength (KCl concentration range 100–300 mM). The topology of the filamentous complexes was investigated with atomic force microscopy. We found that the samples contained distinct, segregated populations of titin molecules and myosin thick filaments. We were unable to identify complexes in which myosin molecules were regularly associated to either mono- or oligomeric titin in either relaxed or stretched states of the titin filaments. Thus, the electrostatically driven self-association is stronger in both myosin and titin than their binding to each other, and it is unlikely that titin functions as a geometrical template for thick-filament formation. However, when allowed to equilibrate configurationally, long myosin thick filaments appeared with titin oligomers attached to their surface. The titin meshwork formed on the thick-filament surface may play a role in controlling thick-filament length by regulating the structural dynamics of myosin molecules and placing a mechanical limit on the filament length.

Original languageEnglish
Pages (from-to)46-53
Number of pages8
JournalJournal of Structural Biology
Volume203
Issue number1
DOIs
Publication statusPublished - Jul 1 2018

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Connectin
Myosins
Sarcomeres
Atomic Force Microscopy
Periodicity

Keywords

  • Atomic force microscopy
  • End-filament
  • Native titin
  • Synthetic myosin filament
  • Template
  • Titin ruler

ASJC Scopus subject areas

  • Structural Biology

Cite this

Topology of interaction between titin and myosin thick filaments. / Kellermayer, M.; Sziklai, Dominik; Papp, Zsombor; Decker, Brennan; Lakatos, Eszter; Mártonfalvi, Zsolt.

In: Journal of Structural Biology, Vol. 203, No. 1, 01.07.2018, p. 46-53.

Research output: Contribution to journalArticle

Kellermayer, M, Sziklai, D, Papp, Z, Decker, B, Lakatos, E & Mártonfalvi, Z 2018, 'Topology of interaction between titin and myosin thick filaments', Journal of Structural Biology, vol. 203, no. 1, pp. 46-53. https://doi.org/10.1016/j.jsb.2018.05.001
Kellermayer, M. ; Sziklai, Dominik ; Papp, Zsombor ; Decker, Brennan ; Lakatos, Eszter ; Mártonfalvi, Zsolt. / Topology of interaction between titin and myosin thick filaments. In: Journal of Structural Biology. 2018 ; Vol. 203, No. 1. pp. 46-53.
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