Figure 8.

Schematic representation of the proposed kindlin-mediated integrin activation mechanism. (A) Integrin remains in a closed conformation when it is not interacting with talin or kindlin (with stable and strong interactions in the IMC and OMC regions). (B) Kindlin alone is unable to disrupt the IMC or OMC interactions and, therefore, unable to induce conformational changes (i.e., angle changes between integrin α- and β-helices) in the transmembrane domain of integrin. (C) Talin binding to the integrin CT causes the complete disruption of OMC and destabilizes IMC interactions. Also, the angle between integrin α and β helices increases significantly upon talin binding. (D) Kindlin interaction with the membrane distal NPXY motif of integrin indirectly pushes talin toward the integrin MP region, resulting in a stronger interaction between talin and the MP motif and a complete disruption of IMC, OMC, and the parallelization of the transmembrane α- and β-helices. To see this figure in color, go online.