Myosin cleft closure determines the energetics of the actomyosin interaction

Balázs Takács, Elizabeth O'Neall-Hennessey, C. Hetényi, J. Kardos, Andrew G. Szent-Györgyi, M. Kovács

Research output: Contribution to journalArticle

16 Citations (Scopus)

Abstract

Formation of the strong binding interaction between actin and myosin is essential for force generation in muscle and in cytoskeletal motor systems. To clarify the role of the closure of myosin's actin-binding cleft in the actomyosin interaction, we performed rapid kinetic, spectroscopic, and calorimetric experiments and atomic-level energetic calculations on a variety of myosin isoforms for which atomic structures are available. Surprisingly, we found that the endothermic actin-binding profile of vertebrate skeletal muscle myosin subfragment-1 is unique among studied myosins. We show that the diverse propensity of myosins for cleft closure determines different energetic profiles as well as structural and kinetic pathways of actin binding. Depending on the type of myosin, strong actin binding may occur via induced-fit or conformational preselection mechanisms. However, cleft closure does not directly determine the kinetics and affinity of actin binding. We also show that cleft closure is enthalpically unfavorable, reflecting the development of an internal strain within myosin in order to adopt precise steric complementarity to the actin filament. We propose that cleft closure leads to an increase in the torsional strain of myosin's central β-sheet that has been proposed to serve as an allosteric energy-transducing spring during force generation.

Original languageEnglish
Pages (from-to)111-121
Number of pages11
JournalFASEB Journal
Volume25
Issue number1
DOIs
Publication statusPublished - Jan 2011

Fingerprint

Actomyosin
Myosins
Actins
Kinetics
Skeletal Muscle Myosins
Myosin Subfragments
Actin Cytoskeleton
Muscle
Vertebrates
Protein Isoforms
Muscles

Keywords

  • Kinetics
  • Mechanism
  • Structure

ASJC Scopus subject areas

  • Biochemistry
  • Biotechnology
  • Genetics
  • Molecular Biology

Cite this

Myosin cleft closure determines the energetics of the actomyosin interaction. / Takács, Balázs; O'Neall-Hennessey, Elizabeth; Hetényi, C.; Kardos, J.; Szent-Györgyi, Andrew G.; Kovács, M.

In: FASEB Journal, Vol. 25, No. 1, 01.2011, p. 111-121.

Research output: Contribution to journalArticle

Takács, Balázs ; O'Neall-Hennessey, Elizabeth ; Hetényi, C. ; Kardos, J. ; Szent-Györgyi, Andrew G. ; Kovács, M. / Myosin cleft closure determines the energetics of the actomyosin interaction. In: FASEB Journal. 2011 ; Vol. 25, No. 1. pp. 111-121.
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