Detachment, futile cycling, and nucleotide pocket collapse in myosin-V stepping

Myosin-V is a highly processive dimeric protein that walks with 36-nm steps along actin tracks, powered by coordinated adenosine triphosphate (ATP) hydrolysis reactions in the two myosin heads. No previous theoretical models of the myosin-V walk reproduce all the observed trends of velocity and run...

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Bibliographic Details
Main Authors: Boon, Neville J. (Author), Hoyle, Rebecca B. (Author)
Format: Article
Language:English
Published: 2015-02-25.
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Online Access:Get fulltext
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100 1 0 |a Boon, Neville J.  |e author 
700 1 0 |a Hoyle, Rebecca B.  |e author 
245 0 0 |a Detachment, futile cycling, and nucleotide pocket collapse in myosin-V stepping 
260 |c 2015-02-25. 
856 |z Get fulltext  |u https://eprints.soton.ac.uk/374800/1/BoonHoyle2015.pdf 
520 |a Myosin-V is a highly processive dimeric protein that walks with 36-nm steps along actin tracks, powered by coordinated adenosine triphosphate (ATP) hydrolysis reactions in the two myosin heads. No previous theoretical models of the myosin-V walk reproduce all the observed trends of velocity and run length with adenosine diphosphate (ADP), ATP and external forcing. In particular, a result that has eluded all theoretical studies based upon rigorous physical chemistry is that run length decreases with both increasing [ADP] and [ATP]. We systematically analyze which mechanisms in existing models reproduce which experimental trends and use this information to guide the development of models that can reproduce them all. We formulate models as reaction networks between distinct mechanochemical states with energetically determined transition rates. For each network architecture, we compare predictions for velocity and run length to a subset of experimentally measured values, and fit unknown parameters using a bespoke Monte Carlo simulated annealing optimization routine. Finally we determine which experimental trends are replicated by the best-fit model for each architecture. Only two models capture them all: one involving [ADP]-dependent mechanical detachment, and another including [ADP]-dependent futile cycling and nucleotide pocket collapse. Comparing model-predicted and experimentally observed kinetic transition rates favors the latter. 
655 7 |a Article