Effect of profilin on actin critical concentration: a theoretical analysis.
To explain the effect of profilin on actin critical concentration in a manner consistent with thermodynamic constraints and available experimental data, we built a thermodynamically rigorous model of actin steady-state dynamics in the presence of profilin. We analyzed previously published mechanisms theoretically and experimentally and, based on our analysis, suggest a new explanation for the effect of profilin. It is based on a general principle of indirect energy coupling. The fluctuation-based process of exchange diffusion indirectly couples the energy of ATP hydrolysis to actin polymerization. Profilin modulates this coupling, producing two basic effects. The first is based on the acceleration of exchange diffusion by profilin, which indicates, paradoxically, that a faster rate of actin depolymerization promotes net polymerization. The second is an affinity-based mechanism similar to the one suggested in 1993 by Pantaloni and Carlier although based on indirect rather than direct energy coupling. In the model by Pantaloni and Carlier, transformation of chemical energy of ATP hydrolysis into polymerization energy is regulated by direct association of each step in the hydrolysis reaction with a corresponding step in polymerization. Thus, hydrolysis becomes a time-limiting step in actin polymerization. In contrast, indirect coupling allows ATP hydrolysis to lag behind actin polymerization, consistent with experimental results.
North Florida/South Georgia Veterans Health System, Research Service, Gainesville, Florida 32610, USA. yarmola@ufl.edu
Elena G
EG
Yarmola
Dmitri A
DA
Dranishnikov
Michael R
MR
Bubb
D008841:Actin Cytoskeleton / Q000187:drug effects / Q000378:metabolism; D000199:Actins / Q000737:chemistry / Q000378:metabolism*; D000244:Adenosine Diphosphate / Q000378:metabolism; D000255:Adenosine Triphosphate / Q000378:metabolism; D000818:Animals; D004058:Diffusion / Q000187:drug effects; D004305:Dose-Response Relationship, Drug; D006801:Humans; D006868:Hydrolysis; D008954:Models, Biological; D010710:Phosphates / Q000494:pharmacology; D051304:Profilins / Q000494:pharmacology*; D011485:Protein Binding / Q000187:drug effects; D055503:Protein Multimerization; D020836:Protein Structure, Quaternary; D011817:Rabbits; D013379:Substrate Specificity; D013816:Thermodynamics
D000199:Actins; D010710:Phosphates; D051304:Profilins; D000244:Adenosine Diphosphate; D000255:Adenosine Triphosphate