Mechano-redox control of integrin de-adhesion

• DOI: 10.7554/elife.34843
• Publication Date: 2018-06-22T12:00:29Z
• Authors: Freda Passam; Joyce Chiu; Lining Ju; Aster Pijning; Zeenat Jahan; Ronit Mor-Cohen; Adva Yeheskel; Katra Kolšek; Lena Thärichen; Camilo Aponte-San...; Frauke Gräter; Philip J Hogg
• Keywords: Force Spectroscopy

How proteins harness mechanical force to control function is a significant biological question. Here we describe human cell surface receptor that couples ligand binding and trigger chemical event which controls the adhesive properties of receptor. Our studies secreted platelet oxidoreductase, ERp5, have revealed it mediates release fibrinogen from activated αIIbβ3 integrin. Protein show extended integrin renders βI-domain Cys177-Cys184 disulfide bond cleavable by ERp5. Fluid shear spectroscopy assays indicate cleavage enhanced force. Cell adhesion molecular dynamics simulations demonstrate induces long-range allosteric effects within βI-domain, mainly affecting metal-binding sites, results in fibrinogen. This coupling binding, redox events may be employed regulate other protein-protein interactions.