Differential binding of ICln in platelets to integrin-derived activating and inhibitory peptides

作者：Raab Markus; Parthasarathi Laavanya; Treumann Achim; Moran Niamh; Daxecker Heide^*

来源：Biochemical and Biophysical Research Communications, 2010, 392(3): 258-263.

DOI：10.1016/j.bbrc.2009.12.088

• Integrin alpha(IIb)beta(3)
• Platelets
• ICln
• Peptide-affinity chromatography
• Protein peptide interaction

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, eg C1B1, 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 f

• 出版日期2010-2-12