Effects of the association of the αv β8 lower legs on integrin ligand binding.

Abstract

Many integrins transmit signals through global conformational changes. However, it is unclear whether integrin αv β8 adopts a similar mechanism during integrin activation and signaling on the cell surface. Here, we showed that disulfide-bonded mutants, which prevented integrin αv β8 lower leg dissociation, bound ligands with similar level as the wild-type protein, suggesting that αv β8 ligand binding did not require lower leg disassociation. We further showed that the N-glycosylation mutant at the interface between the β I and hybrid domains did not affect ligand binding, suggesting that the αv β8 open headpiece was not present on the cell surface. We proposed that αv β8 integrin may adopt only one state, that is, the extended conformation with a closed headpiece. Our results showed that two lower legs retained heterodimeric interfaces, and this association might be important for stabilizing integrin in the extended conformation. Therefore, αv β8 may not transmit bidirectional signals across the plasma membrane but instead may serve as an anchoring site with high affinity and high accessibility for extracellular ligands.