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

Abstract

AbstractIntegrin conformational change is the key to transmitting signals across the cell membrane. The integrin on the cell surface undergoes bending-unbending cycles while sensing and responding to the mechanical environment. Mechanical force triggers the unbending of integrin. However, how an integrin stably extends and how an extended integrin spontaneously bends back are unclear. I performed molecular dynamics simulations on integrin and its subunits to reveal the bending-unbending mechanism of integrin at the atomic level. 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. Thus, 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 the mechanism of how the integrin could achieve the stable extended state.Author summaryAs a mechanosensitive protein, the integrin is a molecular machine, which converts the mechano-signal to others, or in the opposite way. The reversible conformational change of integrin is the key to the mechanosensing function. It is straightforward that the integrin would extend while it senses pulling force. However, how integrin bends back after releasing the force is not clear. The ability to bend back guarantees that the integrin can be reused in the bending-unbending cycles. With molecular dynamics simulations, this study shows the integrin works as a molecular arm in the bending-unbending working cycles, which answers how the integrin spontaneously bends back. Meanwhile, based on this study, several hypothesized mechanisms for integrin to be stably extended are proposed.