Peptides derived from central turn motifs within integrin αIIb and αV cytoplasmic tails inhibit integrin activation

Abstract We previously found that peptides derived from the full length of integrin α IIb and α V cytoplasmic tails inhibited their parent integrin activation, respectively. Here we showed that the cell-permeable peptides corresponding to the conserved central turn motif within α IIb and α V cytoplasmic tails, myr-KRNRPPLEED (α IIb peptide) and myr-KRVRPPQEEQ (α V peptide), similarly inhibited both α IIb and α V integrin activation. Pre-treatment with α IIb or α V peptides inhibited Mn 2+ -activated α IIb β 3 binding to soluble fibrinogen as well as the binding of α IIb β 3 -expressing Chinese Hamster Ovary cells to immobilized fibrinogen. Our turn peptides also inhibited adhesion of two breast cancer cell lines (MDA-MB-435 and MCF7) to α V ligand vitronectin. These results suggest that α IIb and α V peptides share a same mechanism in regulating integrin function. Using α IIb peptide as a model, we found that replacement of RPP with AAA significantly attenuated the inhibitory activity of α IIb peptide. Furthermore, we found that α IIb peptide specifically bound to β-tubulin in cells. Our work suggests that the central motif of α tails is an anchoring point for cytoskeletons during integrin activation and integrin-mediated cell adhesion, and its function depends on the turn structure at RPP. However, post-treatment of peptides derived from the full-length tail or from the turn motif did not reverse α IIb and α V integrin activation.