Response to “On Phosphate Release in Actin Filaments”

Insights into the Cooperative Nature of ATP Hydrolysis in Actin Filaments

“…3), in which the rate of P i release at the interface is approximately the same as the average rate of P i release in the filament, characterized by a variation within 53% relative to the average rate. This is in contrast with the prediction of a strong cooperativity and the resulting implication of an enhancement in rate of P i release at the interface by a factor of 10 6 -10 8 relative to the average rate made in (44), although their analysis ignored any multibody effects beyond a simpler nearestneighbor cooperativity (44,48,49). Clearly, the nature of our predicted cooperativity does not show any signs in support of a purely vectorial ATP hydrolysis or P i release.…”

“…Fitting the predictions of a cooperative model to the time course of polymerization and ATP hydrolysis measured in these experiments eliminates the possibility of the strict vectorial model being accurate in all cases and suggests that the rate of hydrolysis at the ATP-ADP interface must be less than 100 times faster than the rate of hydrolysis away from the interface, although the predictions of a random hydrolysis mechanism were also shown to be able to explain the observed experimental data (42,46). By using the nearest-neighbor cooperativity in such a model as a parameter to fit experimentally measured P i release profiles, it was shown that the possibility of a high degree of cooperativity in P i release could not be completely excluded, however, with some ambiguity in the data analysis involved (41,44,48,49). The random and vectorial models are based on two simple microscopic physical hypotheses that are able to accurately explain the experimental observations.…”

Multiscale simulation of actin filaments and actin-associated proteins

“…Using a mixture of ATP-and ADP-bound G-actin to introduce large number of interfaces in the filament suggested that the rate of hydrolysis at the interface must be less than 100 times faster than the rate of hydrolysis away from the interface, although the predictions of a random hydrolysis mechanism were also shown to be able to explain the observed experimental data (Ohm and Wegner 1994;Pieper and Wegner 1996). By using the nearest-neighbor cooperativity in such a model as a parameter to fit experimentally measured P i release profiles, it was shown that the possibility of a high degree of cooperativity in P i release could not be completely excluded, however with some ambiguity in the data analysis involved (Burnett and Carlsson 2012;Burnett and Carlsson 2013;Jégou et al 2013;Jégou et al 2011).…”

“…A similar contradiction has existed for the P i release reaction, which could be assumed to be either random or cooperative at the filament level. Several attempts have been made to perform a systematic comparison between these views (Burnett and Carlsson 2012; Burnett and Carlsson 2013;Carlier et al 1987;Jégou et al 2013;Korn et al 1987;Ohm and Wegner 1994;Pieper and Wegner 1996;Ranjith et al 2010;Stukalin and Kolomeisky 2006;Vavylonis et al 2005). However, common experimentally measured quantities such as rate of filament elongation, fluctuations in filament length, and size of the un-hydrolyzed ATP cap near the filament end are found to be insensitive to the mechanism of hydrolysis, except for small quantitative difference near critical G-actin concentration.…”