Mechanical regulation of biorecognition: forced unfolding studies of the RGD-containing fibronectin type III10 module

The forced unfolding of fibronectin´s tenth type III module (FnIII ₁₀) was simulated by steered molecular dynamics (SMD) indicating that mechanical tension applied to the module´s termini renders its RGD loop inaccessible to cell surface integrins. FnIII₁₀ possesses a β-sandwich motif consisting of seven β-strands (A-G) that are arranged in two antiparallel sheets with the RGD peptide sequence located at the apex of the FG loop. Computer simulations now reveal that the β-strand G separates from the module at an early stage of unfolding while the remaining fold experiences only small structural perturbations. Consequently, the RGD peptide is pulled closer to the module´s surface as the FG loop unravels. A molecular scale picture of the forced unfolding pathway will be discussed as well as its implications for the understanding of cell-surface interactions