3D structure of amyloid protofilaments of β2-microglobulin fragment probed by solid-state NMR

Kentaro Iwata, Toshimichi Fujiwara, Yoh Matsuki, Hideo Akutsu, Satoshi Takahashi, Hironobu Naiki, Yuji Goto

Research output: Contribution to journalArticlepeer-review

209 Citations (Scopus)


Understanding the structure and formation of amyloid fibrils, the filamentous aggregates of proteins and peptides, is crucial in preventing diseases caused by their deposition and, moreover, for obtaining further insight into the mechanism of protein folding and misfolding. We have combined solid-state NMR, x-ray fiber diffraction, and atomic force microscopy to reveal the 3D structure of amyloid protofilament-like fibrils formed by a 22-residue K3 paptide (Ser20-Lys41) of β2- microglobulin, a protein responsible for dialysis-related amyloidosis. Although a uniformly 13C,15N-labeled sample was used for the NMR measurements, we could obtain the 3D structure of the fibrils on the basis of a large number of structural constraints. The conformation of K3 fibrils was found to be a β-strand-loop-β-strand with each K3 molecule stacked in a parallel and staggered manner. It is suggested that the fibrillar conformation is stabilized by intermolecular interactions, rather than by intramolecular hydrophobic packing as seen in globular proteins. Together with thermodynamic studies of the full-length protein, formation of the fibrils is likely to require side chains on the intermolecular surface to pack tightly against those of adjacent monomers. By revealing the structure of β2- microglobulin protofilament-like fibrils, this work represents technical progress in analyzing amyloid fibrils in general through solid-state MMR.

Original languageEnglish
Pages (from-to)18119-18124
Number of pages6
JournalProceedings of the National Academy of Sciences of the United States of America
Issue number48
Publication statusPublished - 2006 Nov 28


  • 2,2,2-trifluoroethanol
  • Amyloid fibril
  • Dialysis-related amyloidosis
  • Protein misfolding
  • X-ray fiber diffraction


Dive into the research topics of '3D structure of amyloid protofilaments of β2-microglobulin fragment probed by solid-state NMR'. Together they form a unique fingerprint.

Cite this