Myosin dynamics on the millisecond time scale.
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.
Burghardt
Thomas P
TP
Department of Biochemistry and Molecular Biology, Mayo Clinic College of Medicine, Rochester, MN 55905, USA. burghardt@mayo.edu
Hu
Jimmy Yan
JY
Ajtai
Katalin
K
D000255:Adenosine Triphosphate / Q000737:chemistry; D000818:Animals; D002645:Chickens; D006868:Hydrolysis; D009218:Myosins / Q000737:chemistry*; D011487:Protein Conformation; D013050:Spectrometry, Fluorescence; D013816:Thermodynamics; D014364:Tryptophan / Q000737:chemistry
D014364:Tryptophan; D000255:Adenosine Triphosphate; D009218:Myosins