Unique Identification of Supramolecular Structures in Amyloid Fibrils by Solid‐State NMR Spectroscopy

Abstract

The fibril structure formed by the amyloidogenic fragment SNNFGAILSS of the human islet amyloid polypeptide (hIAPP) is determined with 0.52 A resolution. Symmetry information contained in the easily obtainable resonance assignments from solid-state NMR spectra (see picture), along with long-range constraints, can be applied to uniquely identify the supramolecular organization of fibrils.

Relationship between structural composition and material properties of polymorphic hIAPP fibrils

“…homo and hetero), and direction of β strands themselves (i.e. co-aligned and anti-aligned), as shown by Neilson et al [8]. To investigate the relationship between structural compositions based on the organization of each β strand, we considered four basic kinds of polymorphic structures: antiparallel hetero (APHE), antiparallel homo (APHO), parallel hetero (PHE) and parallel homo (PHO) (see Fig.…”

“…films and angled layer structures) with hierarchical compositions of β strands [5]. The existence of amyloid fibrils in these forms can be referred to as polymorphism along with the various compositions and directions of β strands [6][7][8]. Furthermore, the thickness variation of amyloid fibrils as well as the number of protofibril structure were observed [9].…”

Solid‐state NMR detection of 14N13C dipolar couplings between amino acid side groups provides constraints on amyloid fibril architecture

“…3(a)) can be ruled out by these results. It should be noted that the fibril structure of this seeded polymorph is distinct from the fibril structure of the same peptide described by Nielsen et al, [25] illustrating that the polymorphic behaviour of hIAPP 20 -29 is highly sensitive to the growth conditions.…”

Solid-state NMR: An emerging technique in structural biology of self-assemblies

“…Although ssNMR data support anti-parallel stacking for several amyloid fibrils [31,196,220,221], parallel in-register stacking has been experimentally demonstrated in 1998 using MAS ssNMR by Benzinger et al [222] and has since proven to be the more common architecture found in amyloid fibrils [121]. In the optimal case, when the structural homogeneity is high enough to allow for the observation of a single, highly ordered polypeptide conformation, the combination of high-resolution multidimensional ssNMR spectroscopy with different labeling approaches can serve to determine the atomic structures of amyloid fibrils.…”