The interface between the EGF1 and EGF2 domains is critical in integrin affinity regulation.

It has been proposed that integrins adopt a bent, closed conformation with low ligand binding capability at resting state and switch into an extended, open conformation upon activation or interacting with extracellular matrix (ECM) ligand. In this study, we addressed how integrin conformational change at the β genu affects ligand binding and signaling. We discovered that swapping of the β epidermal growth factor-like (EGF) domain 1 and 2 with that of β greatly promoted ligand binding in β β chimeras. Sequence alignment indicated that β integrin uniquely lacks the interface between the EGF1 and 2. Disrupting this interface of the β integrin increased integrin ligand binding. Furthermore, the interface is critical for integrin affinity regulation but not downstream outside-in signaling.