Myosin dynamics on the millisecond time scale

Abstract

Myosin is a motor protein associating with actin and ATP. It translates along actin filaments against a force by transduction of free energy liberated with ATP hydrolysis. Various myosin crystal structures define time points during ATPase showing the protein undergoes large conformation change during transduction over a cycle with approximately 10 ms periodicity. The protein conformation trajectory between two intermediates in the cycle is surmised by non-equilibrium Monte Carlo simulation utilizing free-energy minimization. The trajectory shows myosin transduction of free energy to mechanical work giving evidence for: (i) a causal relationship between product release and work production in the native isoform that is correctly disrupted in a chemically modified protein, (ii) the molecular basis of ATP-sensitive tryptophan fluorescence enhancement and acrylamide quenching, (iii) an actin-binding site peptide containing the free-energy barrier to ATPase product release defining the rate limiting step and, (iv) a scenario for actin-activation of myosin ATPase.

The Myosin C-Loop Is an Allosteric Actin Contact Sensor in Actomyosin

“…ATPase, actin-activated ATPase, active site kinetics, actin binding, and in vitro motility functional tests demonstrate the C-loop plays the central role in mediating active site and actin-binding site communication. These data, together with previous results from nonequilibrium Monte Carlo molecular dynamics (MCMD) simulation elucidating allosteric activation by actin of myosin ATPase (29), suggest that the C-loop is the sensor that when perturbed by actin binding commits myosin to ATP turn over. MCMD simulation suggests the mechanism for commitment to ATP turnover is the simultaneous conformation transition in the two myosin domains spanned by the C-loop to lower the entropic barrier to hydrolysis product release.…”

“…Alternatively, gear peptides make one-residue transitions in one DOF. Previously, we designated the U50a and U50b peptides as U50k and L50k, respectively (29), but have adopted here a new nomenclature to align it with the more conventional terminology. Conventional terminology has the upper 50 kDa domain containing both U50a and U50b while the lower 50 kDa domain contains the gear peptide of amino acids 463–525 and a portion of the loop 2-containing peptide.…”

“…The Gibbs free energy potential change (Δ G ) combines enthalpic (Δ H ) and constant temperature (kelvin) times entropic change ( T Δ S ) in the relationship Δ G = Δ H − T Δ S . We compute the free energy from the separate Δ H and T Δ S components and assign the changes in these quantities to regions in myosin (29). The 20 trajectories simulated for native S1 were mined for information characterizing the energy transduction mechanism.…”

“…They play an important role in the MCMD simulation of myosin trajectory during the M** → M conformation transition (29). U50a encompasses the free energy (mostly entropy-decreasing) barrier to phosphate release, inhibiting myosin ATPase in the absence of actin.…”

Selbstorganisation von Coiled‐Coils in der synthetischen Biologie: Inspiration und Fortschritt

“…[7] Die Motorproteine durchlaufen starke Konformationsänderun-gen, bei denen das dynamische Verhalten der Coiled-CoilDomänen eine entscheidende Rolle spielt. In jedem Bewegungszyklus des Proteins, der einige 10 ms benötigt, [35][36][37][38] ändert sich die Packung der Coiled-Coil-Bereiche auf die einwirkende Kraft hin.…”