Open AccessAllostery and molecular stripping mechanism in profilin regulated actin filament growth
Author(s) -
Weiwei Zhang,
Yi Cao,
Wenfei Li,
Wei Wang
Publication year - 2021
Publication title -
new journal of physics
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 1.584
H-Index - 190
ISSN - 1367-2630
DOI - 10.1088/1367-2630/ac3b2d
Subject(s) - profilin , mdia1 , actin remodeling , protein filament , actin , biophysics , ternary complex , allosteric regulation , actin remodeling of neurons , chemistry , microfilament , microbiology and biotechnology , actin cytoskeleton , biology , biochemistry , cytoskeleton , receptor , cell , enzyme
Profilin is an actin-sequestering protein and plays key role in regulating the polarized growth of actin filament. Binding of profilin to monomeric actin (G-actin) allows continuous elongation at the barbed end (BE), but not the pointed end, of filament. How G-actin exchanges between the profilin-sequestered state and the filament state (F-actin) to support the BE elongation is not well understood. Here, we investigate the involved molecular mechanism by constructing a multi-basin energy landscape model and performing molecular simulations. We showed that the actin exchanging occurs by forming a ternary complex. The interactions arising from the BE binding drive the conformational change of the attached G-actin in the ternary complex from twist conformation to more flatten conformation without involving the change of nucleotide state, which in turn destabilizes the actin–profilin interface and promotes the profilin stripping event through allosteric coupling. We also showed that attachment of free profilin to the BE induces conformational change of the BE actin and facilitates its stripping from the filament. These results suggest a molecular stripping mechanism of the polarized actin filament growth dynamics controlled by the concentrations of the actin–profilin dimer and the free profilin, in which the allosteric feature of the monomeric actin plays crucial role.