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Myosin cleft closure determines the energetics of the actomyosin interaction
Author(s) -
Takács Balázs,
O'NeallHennessey Elizabeth,
Hetényi Csaba,
Kardos József,
SzentGyörgyi Andrew G.,
Kovács Mihály
Publication year - 2011
Publication title -
the faseb journal
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 1.709
H-Index - 277
eISSN - 1530-6860
pISSN - 0892-6638
DOI - 10.1096/fj.10-164871
Subject(s) - myosin , actin , biophysics , chemistry , meromyosin , allosteric regulation , actina , microfilament , myosin head , myosin light chain kinase , crystallography , biochemistry , cytoskeleton , biology , enzyme , cell
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 myo‐sins 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 enthal‐pically 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.—Takacs, B., O'Neall‐Hennessey, E., Hetenyi, C., Kardos, J., Szent‐Gyorgyi, A. G., Kovacs, M. Myosin cleft closure determines the energetics of the actomyosin interaction. FASEBJ. 25, 111–121 (2011). www.fasebj.org