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dept. of structural biology



Solid State NMR

Protein & Amyloid

Protein-Lipid Interaction

SSNMR Methods




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Protein & Amyloid Structure by MAS NMR

Solid state MAS NMR on proteins & protein aggregates

One particular area where solid state magic angle spinning (MAS) NMR is making substantial progress is the area of structure determination on proteins. Progress in both sample preparation and spectroscopic techniques is allowing for better and faster structural measurements. One productive approach is focussed on the preparation of nano- and microcrystals. These tend to be very well ordered, yielding excellent NMR data. At the same time the size requirements for SSNMR are much less demanding than for traditional X-ray crystallographic methods. Other immobilized or aggregated forms of proteins can also be studied, whether through association with membranes, or in amyloid fibrils

The study of amyloid structure and formation is of particular interest, both for its medical significance (being implicated in diseases such as Alzheimer's disorder) and for its more basic contribution to our understanding of protein folding and misfolding. We apply MAS SSNMR structural methods both to study disease-related fibril forms but also to tackle fundamental questions related to amyloid fibril formation.

Case study - SSNMR of amyloid peptide nanocrystals & fibrils

As an illustration of the capabilities of SSNMR in this area: The GNNQQNY7-13 peptideGNNQQNY monoclinic crystal x-ray structure fragment of the yeast prion protein Sup35p forms  both (nano)crystals and amyloid-like fibrils, and has developed into a popular model system for computational studies of amyloid formation.This is in part due to the availability of crystal structures, which are proposed to reflect structural features common of amyloid fibrils.  MAS SSNMR allows direct comparisons between crystals and fibrils [3]. (See also an earlier publication on DNP enhancement of the crystalline material: [2])


The figures above show both transmission electron microscopy (TEM) data on the crystals and fibrils (a). Note that even the crystals are very small. The panels to the right (b) show the (color coded) resonance positions in a two-dimensional solid state MAS NMR experiment on both types of samples (for a segmentally labeled peptide GNNQQNY; underlined = 13C,15N-labeled). The relatively narrow peaks in the NMR data indicate that the crystals and fibrils have well-defined conformations and we see a high beta-sheet content. Interestingly the fibrils reproducibly gives three sets of signals indicating the presence of three distinct structural forms within the fibril samples. These experiments allow site-specific studies, even in the presence of mixed conformers, and highlight a much increased structural and dynamical complexity in the fibrils.


  1. Nelson, R. et al. (2005) Structure of the cross-beta spine of amyloid-like fibrils. Nature 435, 773-778.
  2. Van  der Wel, P.C.A. et al. (2006) Dynamic nuclear polarization of amyloidogenic peptide nanocrystals: GNNQQNY, a core segment of the yeast prion protein Sup35p. J. Am. Chem. Soc. 128: 10840-10846  *
  3. Van der Wel, P.C.A. et al. (2007) Solid state NMR study of amyloid nanocrystals and fibrils formed by the peptide GNNQQNY from yeast prion protein Sup35p. J. Am. Chem. Soc. 129: 5117-5130. *