Mechanical regulation of biorecognition: forced unfolding studies of the RGD-containing fibronectin type III{sub}10 module

摘要

The forced unfolding of fibronectin's tenth type III module (FnIII{sub}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 surfaceintegrins. FnIII{sub}10 possesses a β-sandwich motif consisting of seven β-strands (A-G) that are arranged in two anti-parallel 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.