Figure 2.

Schematic of the integrin activation conformational changes and key modulators: Resting integrins have a bent low-affinity (E⁻H⁻) conformation. They attain an extended low-affinity (E⁺H⁻) confirmation through the RIAM- and Rap1-mediated recruitment of talin-1. Further recruitment of kindlin-3 induces full integrin activation into extended high-affinity integrins (E⁺H⁺). There is an alternative allosteric pathway in which E⁻H⁻ integrins transition to a bent-high affinity conformation (E⁻H⁺) and then change to an extended high-affinity integrin (E⁺H⁺). Which integrin adaptors are involved in this allosteric pathway remains to be further investigated. Created in BioRender.com (accessed on 12 June 2022).