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Single protein misfolding events captured by atomic force microscopy

Nature Structural Biology volume 6, pages 1025–1028 (1999)Cite this article

Abstract

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.

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Figure 1: Reversible misfolding events captured by single protein AFM recordings of a polyprotein composed of tandem repeats of an immunoglobulin domain.
Figure 2: Unfolding of a 'skip' fold lengthens the contour length of the polyprotein by more than the simultaneous unfolding of two domains.
Figure 3: Folded polyproteins that harbor a 'skip' fold are shorter than correctly folded ones.
Figure 4: Misfolding events observed during mechanical unfolding/refolding cycles of the extracellular matrix protein tenascin.

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Acknowledgements

We would like to thank H.P. Erickson (Duke University) for providing the human tenascin protein. This work was supported by NIH grants to J.M.F., P.E.M. and A.F.O.

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Authors and Affiliations

  1. Department of Physiology and Biophysics, Mayo Foundation, Rochester, 55905, Minnesota, USA

    Andres F. Oberhauser, Piotr E. Marszalek, Mariano Carrion-Vazquez & Julio M. Fernandez

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  1. Andres F. Oberhauser
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  2. Piotr E. Marszalek
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  3. Mariano Carrion-Vazquez
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  4. Julio M. Fernandez
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Correspondence to Julio M. Fernandez.

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Oberhauser, A., Marszalek, P., Carrion-Vazquez, M. et al. Single protein misfolding events captured by atomic force microscopy . Nat Struct Mol Biol 6, 1025–1028 (1999). https://doi.org/10.1038/14907

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