Structure-functional analysis of peptide p3 identical to γ370-383, binding sites with integrin α_iibβ₃ γc-domain of fibrinogen

The interactions between platelet integrin α_IIbβ ₃ and fibrinogen (Fg) mediate a range of adhesive reactions, which are necessary for platelet aggregation and fibrin clot retraction. The binding site for α,_IIbβ₃ resides in the γC domain of Fg. In our previous work we have identified a novel binding site in the γC domain, γ370-383 (P3), for integrin α _IIbα₃ and have demonstrated that the P3 sequence together with the C-terminal γC sequence ⁴⁰⁸AGDV⁴¹¹ accounts for the full binding of α_IIbβ₃. In our present study, in order to define the amino acid residues in P3 involved in the interaction with α_IIbβ₃, we have used SPOT-synthesis analyses. Libraries consisting of peptides covering P3 were created and probed with radiolabeled α_IIbβ₃. Screening of the libraries showed that several positively charged residues may be critical for interaction of P3 with integrin α_IIbβ ₃.