Inside the leading edge of a crawling cell, intricate networks of rod-like actin filaments extend toward the cell membrane at various angles, lengthening protein by protein. Upon impact, the crisscrossing rods glance off the membrane and bend as the collective force of myriad filaments pushes the cell forward.

How flexible these filaments are, and how effectively they recruit essential regulatory proteins to their cause, depends on the properties of the individual actin proteins composing them. Now, a new study in Nature provides high-resolution structures showing how two key biochemical states of actin work jointly with bending forces to determine how actin can interact with other proteins.

“When you add force to the mix, you see substantial changes,” says Rockefeller’s Gregory Alushin. “We provide clear evidence that these biochemical changes in actin are only readable through the mechanical properties of the filaments.”

Revisiting protein control

Actin filaments are long polymers of actin proteins, linked end to end. Actin proteins within a filament can exist in one of two important biochemical states. Actin newly added to the polymer contains a phosphate molecule and aged actin does not; otherwise, the two states are more or less identical. But actin-binding proteins can tell them apart, and they will bind or ignore a filament based on the state of its actin.

How actin-binding proteins distinguish between these states is a long-standing mystery. Some have proposed that phosphate somehow changes the shape of actin, allowing actin-binding proteins to pick it out of the crowd in vivo. Indeed, many enzymes can switch between shapes when other molecules latch onto them, in a process known as allosteric regulation. It made some sense to assume that actin would be no different.

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