Using single protein atomic force microscopy (AFM) techniques we demonstrate
that after repeated mechanical extension/relaxation cycles, tandem modular
proteins can misfold into a structure formed by two neighboring modules. The
misfolding is fully reversible and alters the mechanical topology of the modules
while it is about as stable as the original fold. Our results show that modular
proteins can assume a novel misfolded state and demonstrate that AFM is able
to capture, in real time, rare misfolding events at the level of a single
protein.
