The capacity of platelets to form a
thrombus is mediated by
integrin alpha(IIb)beta(3). The cytoplasmic tail of alpha(IIb) contains a highly conserved motif, (989)KVGFFKR(995), which plays a critical role in regulating
integrin activation and acts as a recognition site for various intracellular
proteins, e.g. CIB1, PP1, ICln and RN181. Previously, we demonstrated that a cell-permeable
integrin-derived activating (IDA)
peptide, KVGFFKR, induces platelet activation, whereas an
integrin-derived inhibitory (IDI)
peptide, KVGAAKR, is antithrombotic. To elucidate the molecular mechanism underlying these opposite effects we investigate the affinity of known
integrin alpha(IIb)
binding proteins for the two immobilized
peptides in dependence on the activation state of platelets by means of
peptide-affinity chromatography, blotting techniques and
protein:
peptide docking studies. Our results provide a model for the inhibition of ICln interaction with the
integrin in activated platelets by the IDI-
peptide. Thus, ICln:IDI-
peptide interaction profiles can have a pivotal purpose in the search for consensus pharmacophores specifically inhibiting ICln function in platelets potentially leading to the development of
integrin-derived antithrombotic drugs.