Structural Biology

Form and Function

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Science  12 Jul 2013:
Vol. 341, Issue 6142, pp. 110-111
DOI: 10.1126/science.341.6142.110-d

Formins are involved in regulating actin polymerization by nucleating new actin filaments and promoting elongation at the filament barbed end. In formins, a donut-shaped dimer of FH2 domains encircles the barbed end of the filament, and the FH1 domain binds profilin-actin complexes and rapidly transfers actin monomers to the barbed end. The FH2 dimer gates polymerization by transitioning between an open and a closed state, with the open state favoring actin monomer binding. Many formin-mediated actin structures experience tension, but how this affects formin function is unclear. Courtemanche et al. explored the effect of tension on actin polymerization induced by yeast formin Bni1p. Formin was anchored to a lipid bilayer through its N terminus, and buffer flow was used to align initiated filaments into “actin curtains.” It has previously been proposed that tension might favor polymerization, by increasing the FH2 domain stepping rate, but limit the enhancement in rate provided by profilin by slowing the transfer of profilin-actin to the barbed end. Courtemanche et al. found the opposite—small forces slowed formin-mediated polymerization in the absence of profilin but increased the rate of polymerization in its presence. Simulations were consistent with the proposal that tension favors the closed state of the FH2 dimer, but profilin-actin bound to the FH1 domain allosterically shifts the FH2 equilibrium toward the open state.

Proc. Natl. Acad. Sci. U.S.A. 110, 9752 (2013).

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