2M4J

40-residue beta-amyloid fibril derived from Alzheimer's disease brain

Summary for 2M4J

• Entry DOI: 10.2210/pdb2m4j/pdb
• NMR Information: BMRB: 19009
• Descriptor: Amyloid beta A4 protein (1 entity in total)
• Functional Keywords: amyloid, alzheimer's disease, solid state nmr, protein fibril
• Biological source: Homo sapiens (human)
• Cellular location: Membrane; Single-pass type I membrane protein: P05067
• Total number of polymer chains: 9
• Total formula weight: 39022.67

Authors

Lu, J.,Qiang, W.,Meredith, S.C.,Yau, W.,Schweiters, C.D.,Tycko, R. (deposition date: 2013-02-05, release date: 2013-09-25, Last modification date: 2024-05-15)

Primary citation

Lu, J.X.,Qiang, W.,Yau, W.M.,Schwieters, C.D.,Meredith, S.C.,Tycko, R.
Molecular Structure of beta-Amyloid Fibrils in Alzheimer's Disease Brain Tissue.
Cell(Cambridge,Mass.), 154:1257-1268, 2013

PubMed Abstract: In vitro, β-amyloid (Aβ) peptides form polymorphic fibrils, with molecular structures that depend on growth conditions, plus various oligomeric and protofibrillar aggregates. Here, we investigate structures of human brain-derived Aβ fibrils, using seeded fibril growth from brain extract and data from solid-state nuclear magnetic resonance and electron microscopy. Experiments on tissue from two Alzheimer's disease (AD) patients with distinct clinical histories showed a single predominant 40 residue Aβ (Aβ40) fibril structure in each patient; however, the structures were different from one another. A molecular structural model developed for Aβ40 fibrils from one patient reveals features that distinguish in-vivo- from in-vitro-produced fibrils. The data suggest that fibrils in the brain may spread from a single nucleation site, that structural variations may correlate with variations in AD, and that structure-specific amyloid imaging agents may be an important future goal.

PubMed: 24034249
DOI: 10.1016/j.cell.2013.08.035

Experimental method

SOLID-STATE NMR