Single protein misfolding events captured by atomic force microscopy.
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.
Oberhauser
A F
AF
Department of Physiology and Biophysics, Mayo Foundation, Rochester, Minnesota 55905, USA.
Marszalek
P E
PE
Carrion-Vazquez
M
M
Fernandez
J M
JM
D064211:Connectin; D006801:Humans; D007136:Immunoglobulins / Q000737:chemistry*; D018625:Microscopy, Atomic Force; D009124:Muscle Proteins / Q000737:chemistry*; D009206:Myocardium / Q000737:chemistry; D020815:Polyproteins / Q000737:chemistry* / Q000235:genetics / Q000378:metabolism* / Q000648:ultrastructure; D011489:Protein Denaturation; D015202:Protein Engineering; D017510:Protein Folding; D011494:Protein Kinases / Q000737:chemistry*; D020673:Protein Renaturation; D017433:Protein Structure, Secondary; D017434:Protein Structure, Tertiary; D020449:Repetitive Sequences, Amino Acid
D064211:Connectin; D007136:Immunoglobulins; D009124:Muscle Proteins; D020815:Polyproteins; C577285:TTN protein, human; D011494:Protein Kinases