Gating mechanisms during actin filament elongation by formins

eLife

Naomi Courtemanche¹  Thomas D Pollard²  Fikret Aydin³  Gregory A Voth⁴ 

[1] Institute for Biophysical Dynamics, The University of Chicago, Chicago, United States;James Franck Institute, The University of Chicago, Chicago, United States;Department of Chemistry, The University of Chicago, Chicago, United States;Department of Genetics, Cell Biology and Development, University of Minnesota, Minneapolis, United States;

关键词: formin;    FH2 domain;    gating mechanism;    coarse-grained;    molecular dynamics;    intermolecular interactions;   

DOI  :  10.7554/eLife.37342

来源: DOAJ

【 摘 要 】

Formins play an important role in the polymerization of unbranched actin filaments, and particular formins slow elongation by 5–95%. We studied the interactions between actin and the FH2 domains of formins Cdc12, Bni1 and mDia1 to understand the factors underlying their different rates of polymerization. All-atom molecular dynamics simulations revealed two factors that influence actin filament elongation and correlate with the rates of elongation. First, FH2 domains can sterically block the addition of new actin subunits. Second, FH2 domains flatten the helical twist of the terminal actin subunits, making the end less favorable for subunit addition. Coarse-grained simulations over longer time scales support these conclusions. The simulations show that filaments spend time in states that either allow or block elongation. The rate of elongation is a time-average of the degree to which the formin compromises subunit addition rather than the formin-actin complex literally being in ‘open’ or ‘closed’ states.

【 授权许可】

Unknown