Single protein misfolding events captured by atomic force microscopy

Using single protein atomic force microscopy (AFM) techniques we demonstrat e that after repeated mechanical extension/relaxation cycles, tandem modula r proteins tan misfold into a structure formed by two neighboring modules. The misfolding is fully reversible and alters the mechanical topology of th e modules while it is about as stable as the original fold. Our results sho w 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 le vel of a single protein.