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A Mechanistic Model of the Actin Cycle

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dc.contributor.author Bindschadler, M.
dc.contributor.author Osborn, E. A.
dc.contributor.author Dewey, C. F. Jr
dc.contributor.author McGrath, J. L.
dc.date.accessioned 2005-09-01T12:00:00Z en_US
dc.date.available 2005-09-01T12:00:00Z en_US
dc.date.issued 2004-05
dc.identifier.uri http://hdl.handle.net/1721.1/26696
dc.description Biophysical Journal, 2004 en
dc.description.abstract We have derived a broad, deterministic model of the steady-state actin cycle that includes its major regulatory mechanisms. Ours is the first model to solve the complete nucleotide profile within filaments, a feature that determines the dynamics and geometry of actin networks at the leading edges of motile cells, and one that has challenged investigators developing models to interpret steady-state experiments. We arrived at the nucleotide profile through analytic and numerical approaches that completely agree. Our model reproduces behaviors seen in numerous experiments with purified proteins, but allows a detailed inspection of the concentrations and fluxes that might exist in these experiments. These inspections provide new insight into the mechanisms that determine the rate of actin filament treadmilling. Specifically, we find that mechanisms for enhancing Pi release from the ADP-Pi intermediate on filaments, for increasing the off rate of ADP-bound subunits at pointed ends, and the multiple, simultaneous functions of profilin, make unique and essential contributions to increased treadmilling. In combination, these mechanisms have a theoretical capacity to increase treadmilling to levels limited only by the amount of available actin. This limitation arises because as the cycle becomes more dynamic, it tends toward the unpolymerized state. en
dc.format.extent 364500 bytes
dc.format.mimetype application/pdf
dc.language.iso en_US en
dc.publisher Biophysical Society en
dc.subject Actin Cycle en
dc.subject nucleotide profile en
dc.subject actin filament en
dc.title A Mechanistic Model of the Actin Cycle en
dc.type Article en
dc.identifier.citation Biophysical Journal, 86, p. 2720-2739, (2004) en


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