Protein Misfolding

  • Marie-Theres Hutchison
  • Harald Schwalbe
Reference work entry


Normal protein function is essential for cellular processes. This is dependent on proteins adopting a native conformation. Misfolding of proteins is implicated in several devastating human diseases. A variety of ways in which a protein can be misfolded are recognized and include: proteins that are unable to fold, those which adopt toxic folds, and those which mislocalize due to misfolding to name a few. Characterization of such misfolding proteins, which are often of a highly dynamic nature, can be challenging. Structural insights can be gleaned from CD, SEC, SDS, and native PAGE, SAXS, TEM, DLS, ThT, and MS – albeit not in atomic detail. Although structure elucidation of static complexes could be investigated by X-ray, no detail can be extracted for regions of intrinsic disorder (which happen to be commonplace in misfolding protein systems). NMR is the most suitable technique in studying misfolding systems offering a wide range of techniques for the characterization of both the structural and dynamic aspects connected with protein misfolding diseases.


Amyloid Aggregation Intrinsically Disordered Protein Labeling Misfolding Nuclear Magnetic Resonance 



Circular dichroism




Dark-state exchange saturation transfer


Dynamic light scattering


Electron microscopy




Intrinsically disordered protein


Intrinsically disordered region


Insensitive nuclei enhanced by polarization transfer


In-phase anti-phase

kDa, MDa

Kilo Dalton, mega Dalton


Laser-induced liquid bead ion desorption mass spectrometry


Magic angle spinning




Molecular weight


Nuclear magnetic resonance


Nuclear overhauser enhancement


Paramagnetic relaxation enhancement


Residual dipolar couplings


Small angle X-ray scattering


Sodium dodecyl sulfate polyacrylamide gel electrophoresis


Size exclusion chromatography


Sedimented solutes NMR


Thioflavin T fluorescence


Transverse relaxation optimized spectroscopy




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Copyright information

© Springer International Publishing AG, part of Springer Nature 2018

Authors and Affiliations

  • Marie-Theres Hutchison
    • 2
  • Harald Schwalbe
    • 1
  1. 1.Institute of Organic Chemistry and Chemical Biology, Center for Biomolecular Magnetic Resonance (BMRZ)Goethe University FrankfurtFrankfurt am MainGermany
  2. 2.Institute for Organic Chemistry and Chemical Biology, Center for Biomolecular Magnetic ResonanceJohann Wolfgang Goethe-UniversitätFrankfurt/MGermany

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