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Protein Misfolding

  • Marie-Theres Hutchison
  • Harald Schwalbe
Reference work entry

Abstract

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.

Keywords

Amyloid Aggregation Intrinsically Disordered Protein Labeling Misfolding Nuclear Magnetic Resonance 

Abbreviations

CD

Circular dichroism

CP

Cross-polarization

DEST

Dark-state exchange saturation transfer

DLS

Dynamic light scattering

EM

Electron microscopy

H/D

Hydrogen/deuterium

IDP

Intrinsically disordered protein

IDR

Intrinsically disordered region

INEPT

Insensitive nuclei enhanced by polarization transfer

IPAP

In-phase anti-phase

kDa, MDa

Kilo Dalton, mega Dalton

LILBID MS

Laser-induced liquid bead ion desorption mass spectrometry

MAS

Magic angle spinning

MSTL

Methanethiosulfonate

MW

Molecular weight

NMR

Nuclear magnetic resonance

NOE

Nuclear overhauser enhancement

PRE

Paramagnetic relaxation enhancement

RDC

Residual dipolar couplings

SAXS

Small angle X-ray scattering

SDS-PAGE

Sodium dodecyl sulfate polyacrylamide gel electrophoresis

SEC

Size exclusion chromatography

sedNMR

Sedimented solutes NMR

ThT

Thioflavin T fluorescence

TROSY

Transverse relaxation optimized spectroscopy

UC

Ultracentrifugation

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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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