Actin as a Tension Sensor

Abstract

An unsolved puzzle has been why the sequences of all eukaryotic actins have been so exquisitely conserved over large evolutionary distances, but the bacterial actin-like proteins show no such sequence conservation, and have diverged so much that many are as different from each other as they are from eukaryotic actin. We can show that actin filaments exhibit large amounts of cooperativity in structural states, as well as allosteric relationships within the subunit. Interestingly, some of the most dramatic allosteric couplings involve elements in actin that are not present in the bacterial actin-like proteins, such as the N-terminus, the C-terminus, the DNase I-binding loop, and the “hydrophobic plug”. We suggest that these insertions provide for the extraordinary properties of actin, allowing actin filaments to form highly organized structures such as muscle sarcomeres, stereocilia of the inner ear, microvilli, stress fibers, etc. In contrast, the bacterial ParM protein forms a very different filament than F-actin, which accounts for why that filament behaves very differently: it shows dynamic instability, and the growth at the two ends is very similar. While biochemists have typically focused on how small molecules, pH, and other proteins modulate the activity of a protein of interest, it is clear that mechanical forces can play a large role. We provide some new insights into the mechanical properties of F-actin, and suggest how actin can act as a tension sensor in many cell biological systems. In contrast to the long held view that F-actin is almost inextensible, we show how subdomain 2 of actin cooperatively and allosterically modulates both the bending and stretching stiffness of F-actin. Further, we show that the ability of actin-binding proteins to change actin's structure depends upon the intrinsic plasticity and cooperativity of actin.