2e8d
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3D Structure of amyloid protofilaments of beta2-microglobulin fragment probed by solid-state NMR
OverviewOverview
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 peptide (Ser(20)-Lys(41)) of, beta(2)-microglobulin, a protein responsible for dialysis-related, amyloidosis. Although a uniformly (13)C,(15)N-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 beta-strand-loop-beta-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 beta(2)-microglobulin protofilament-like, fibrils, this work represents technical progress in analyzing amyloid, fibrils in general through solid-state NMR.
DiseaseDisease
Known disease associated with this structure: Hypoproteinemia, hypercatabolic OMIM:[109700]
About this StructureAbout this Structure
2E8D is a Single protein structure of sequence from Homo sapiens. Full crystallographic information is available from OCA.
ReferenceReference
3D structure of amyloid protofilaments of beta2-microglobulin fragment probed by solid-state NMR., Iwata K, Fujiwara T, Matsuki Y, Akutsu H, Takahashi S, Naiki H, Goto Y, Proc Natl Acad Sci U S A. 2006 Nov 28;103(48):18119-24. Epub 2006 Nov 15. PMID:17108084
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