A molecular arm: the molecular bending–unbending mechanism of integrin

Abstract

The balance of integrin activation and deactivation regulates its function and mediates cell behaviors. Mechanical force triggers the unbending and activation of integrin. However, how an activated and extended integrin spontaneously bends back is unclear. I performed all-atom molecular dynamics simulations on an integrin or its subunits to reveal the bending-unbending mechanism of integrin. According to the simulations, the integrin structure works like a human arm. The integrin α subunit serves as the bones, while the β leg serves as the bicep. The integrin extension results in the stretching of the β leg, and the extended integrin spontaneously bends as a consequence of the contraction of the β leg. This study provides new insights into the mechanism of how the integrin secures in the bent inactivated state and sheds light on how the integrin could achieve a stable extended state.