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

Abstract

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 β3 epidermal growth factor-like (EGF) domain 1 and 2 with that of β8 greatly promoted ligand binding in β3 β8 chimeras. Sequence alignment indicated that β8 integrin uniquely lacks the interface between the EGF1 and 2. Disrupting this interface of the β3 integrin increased integrin ligand binding. Furthermore, the interface is critical for integrin affinity regulation but not downstream outside-in signaling.