ACTIN POLYMERIZATION AND DE-POLYMERIZATION COUPLED TO RANDOM HYDROLYSIS: BROWNIAN DYNAMICS

摘要

Actin polymerization is coupled with adenosine triphosphate (ATP) hydrolysis into adenosine diphosphate (ADP) and inorganic phosphate (Pi) release, and then actin protomers attain three different states corresponding to a bound ATP, ADP/Pi, and ADP molecule. A single filament allowed to assemble in a bath of constant concentration of free ATP-actin monomers, C_T, is studied by Brownian dynamics simulation. When the ATP-actin concentration is between the critical concentration of the barbed and pointed end, actin filament is located in a state of 'treadmilling'. The main propose in the present study is to provide the non-equilibrium description of actin filament The phenomenological relations are addressed between waiting times, treadmilling flux and growth flux. We also find that global fluxes, such as growth flux, ATP cleavage flux and Pi release flux, are closely concerned with spatial patterns of protomer domains and domain boundary, such as ATPactin and ADP/Pi-actin caps at both filament ends. Introduction The dynamical-assembly processes of actin proteins (or G-actin) into actin filaments, play fundamental roles in many biological processes, such as cell division, motility, reproduction and endocytosis~(14). The mechanism of actin dynamics in cells is coupled to irreversible ATP hydrolysis which involves three nucleotide states of each actin protomers. The three nucleotide states of actin protomers have different conformations and then exhibit different attachment and detachment rates. Because of the intrinsic polarity of actin protomer within a filament, the two-stranded helical filament has two distinct ends, a barbed, fast growing end and a pointed, slow shrinking end. At steady state, the two ends of the filament differ in their chemical compositions, and are not in universal chemical equilibrium, but in a 'treadmilling' process with monomeric actins attached to the barbed end and detached from the other pointed end5. ATP hydrolysis therefore provides the chemical energy from an inherently non-equilibrium phenomenon 'treadmilling'.